Predictors of responses to immune checkpoint blockade in advanced melanoma.
Identifieur interne : 000487 ( PubMed/Curation ); précédent : 000486; suivant : 000488Predictors of responses to immune checkpoint blockade in advanced melanoma.
Auteurs : N. Jacquelot [France] ; M P Roberti [France] ; D P Enot [France] ; S. Rusakiewicz [France] ; N. Ternès [France] ; S. Jegou [France] ; D M Woods [États-Unis] ; A L Sodré [États-Unis] ; M. Hansen [Danemark] ; Y. Meirow [Israël] ; M. Sade-Feldman [Israël] ; A. Burra [États-Unis] ; S S Kwek [États-Unis] ; C. Flament [France] ; M. Messaoudene [France] ; C P M. Duong [France] ; L. Chen [États-Unis] ; B S Kwon [Corée du Sud] ; A C Anderson [États-Unis] ; V K Kuchroo [États-Unis] ; B. Weide [Allemagne] ; F. Aubin [France] ; C. Borg [France] ; S. Dalle [France] ; O. Beatrix [France] ; M. Ayyoub [France] ; B. Balme [France] ; G. Tomasic [France] ; A M Di Giacomo [Italie] ; M. Maio [Italie] ; D. Schadendorf [Allemagne] ; I. Melero [Espagne] ; B. Dréno [France] ; A. Khammari [France] ; R. Dummer [Suisse] ; M. Levesque [Suisse] ; Y. Koguchi [États-Unis] ; L. Fong [États-Unis] ; M. Lotem [Israël] ; M. Baniyash [Israël] ; H. Schmidt [Danemark] ; I M Svane [Danemark] ; G. Kroemer [France] ; A. Marabelle [France] ; S. Michiels [France] ; A. Cavalcanti [France] ; M J Smyth [Australie] ; J S Weber [États-Unis] ; A M Eggermont [France] ; L. Zitvogel [France]Source :
- Nature communications [ 2041-1723 ] ; 2017.
Abstract
Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we retrospectively observed, in eight cohorts enrolling 190 MMel patients treated with ipilimumab, that PD-L1 expression on peripheral T cells was prognostic on overall and progression-free survival. Moreover, detectable CD137 on circulating CD8(+) T cells was associated with the disease-free status of resected stage III MMel patients after adjuvant ipilimumab + nivolumab (but not nivolumab alone). These biomarkers should be validated in prospective trials in MMel.The clinical management of metastatic melanoma requires predictors of the response to checkpoint blockade. Here, the authors use immunological assays to identify potential prognostic/predictive biomarkers in circulating blood cells and in tumor-infiltrating lymphocytes from patients with resected stage III melanoma.
DOI: 10.1038/s41467-017-00608-2
PubMed: 28928380
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Balme</name><affiliation wicri:level="1"><nlm:affiliation>Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon and University Claude Bernard Lyon 1, Lyon, 69000, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon and University Claude Bernard Lyon 1, Lyon, 69000</wicri:regionArea></affiliation></author><author><name sortKey="Tomasic, G" sort="Tomasic, G" uniqKey="Tomasic G" first="G" last="Tomasic">G. Tomasic</name><affiliation wicri:level="1"><nlm:affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Gustave Roussy Cancer Campus, Villejuif, 94800</wicri:regionArea></affiliation></author><author><name sortKey="Di Giacomo, A M" sort="Di Giacomo, A M" uniqKey="Di Giacomo A" first="A M" last="Di Giacomo">A M Di Giacomo</name><affiliation wicri:level="1"><nlm:affiliation>Medical Oncology and Immunotherapy Division, University Hospital of Siena, Viale Bracci, 14, Siena, 53100, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Medical Oncology and Immunotherapy Division, University Hospital of Siena, Viale Bracci, 14, Siena, 53100</wicri:regionArea></affiliation></author><author><name sortKey="Maio, M" sort="Maio, M" uniqKey="Maio M" first="M" last="Maio">M. Maio</name><affiliation wicri:level="1"><nlm:affiliation>Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Instituto Toscano Tumori, Siena, 53100, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Instituto Toscano Tumori, Siena, 53100</wicri:regionArea></affiliation></author><author><name sortKey="Schadendorf, D" sort="Schadendorf, D" uniqKey="Schadendorf D" first="D" last="Schadendorf">D. Schadendorf</name><affiliation wicri:level="1"><nlm:affiliation>Department of Dermatology, University Hospital, University Duisburg-Essen, Essen, Germany & German Cancer Consortium (DKTZ), Heidelberg, D-69120, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, University Hospital, University Duisburg-Essen, Essen, Germany & German Cancer Consortium (DKTZ), Heidelberg, D-69120</wicri:regionArea></affiliation></author><author><name sortKey="Melero, I" sort="Melero, I" uniqKey="Melero I" first="I" last="Melero">I. Melero</name><affiliation wicri:level="1"><nlm:affiliation>Division of Gene Therapy and Hepatology, Centre for Applied Medical Research, Pamplona, 31008, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Division of Gene Therapy and Hepatology, Centre for Applied Medical Research, Pamplona, 31008</wicri:regionArea></affiliation></author><author><name sortKey="Dreno, B" sort="Dreno, B" uniqKey="Dreno B" first="B" last="Dréno">B. Dréno</name><affiliation wicri:level="1"><nlm:affiliation>Department of Onco-dermatology, CIC Biotherapy, INSERM U1232, CHU Nantes, Nantes, 44000, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Onco-dermatology, CIC Biotherapy, INSERM U1232, CHU Nantes, Nantes, 44000</wicri:regionArea></affiliation></author><author><name sortKey="Khammari, A" sort="Khammari, A" uniqKey="Khammari A" first="A" last="Khammari">A. Khammari</name><affiliation wicri:level="1"><nlm:affiliation>Department of Onco-dermatology, CIC Biotherapy, INSERM U1232, CHU Nantes, Nantes, 44000, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Onco-dermatology, CIC Biotherapy, INSERM U1232, CHU Nantes, Nantes, 44000</wicri:regionArea></affiliation></author><author><name sortKey="Dummer, R" sort="Dummer, R" uniqKey="Dummer R" first="R" last="Dummer">R. Dummer</name><affiliation wicri:level="1"><nlm:affiliation>Department of Dermatology, University Hospital Zürich and University of Zürich, Zürich, 8091, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Dermatology, University Hospital Zürich and University of Zürich, Zürich, 8091</wicri:regionArea></affiliation></author><author><name sortKey="Levesque, M" sort="Levesque, M" uniqKey="Levesque M" first="M" last="Levesque">M. Levesque</name><affiliation wicri:level="1"><nlm:affiliation>Department of Dermatology, University Hospital Zürich and University of Zürich, Zürich, 8091, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Dermatology, University Hospital Zürich and University of Zürich, Zürich, 8091</wicri:regionArea></affiliation></author><author><name sortKey="Koguchi, Y" sort="Koguchi, Y" uniqKey="Koguchi Y" first="Y" last="Koguchi">Y. Koguchi</name><affiliation wicri:level="1"><nlm:affiliation>Earle A. Chiles Research Institute, Providence Cancer Center, Portland, OR, 97213, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Earle A. Chiles Research Institute, Providence Cancer Center, Portland, OR, 97213</wicri:regionArea></affiliation></author><author><name sortKey="Fong, L" sort="Fong, L" uniqKey="Fong L" first="L" last="Fong">L. 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Schmidt</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, Aarhus University Hospital, Aarhus, DK-8200, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Department of Oncology, Aarhus University Hospital, Aarhus, DK-8200</wicri:regionArea></affiliation></author><author><name sortKey="Svane, I M" sort="Svane, I M" uniqKey="Svane I" first="I M" last="Svane">I M Svane</name><affiliation wicri:level="1"><nlm:affiliation>Center for Cancer Immune Therapy, Department of Hematology and Oncology, Copenhagen University Hospital, Herlev, DK-2730, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Center for Cancer Immune Therapy, Department of Hematology and Oncology, Copenhagen University Hospital, Herlev, DK-2730</wicri:regionArea></affiliation></author><author><name sortKey="Kroemer, G" sort="Kroemer, G" uniqKey="Kroemer G" first="G" last="Kroemer">G. Kroemer</name><affiliation wicri:level="1"><nlm:affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Gustave Roussy Cancer Campus, Villejuif, 94800</wicri:regionArea></affiliation></author><author><name sortKey="Marabelle, A" sort="Marabelle, A" uniqKey="Marabelle A" first="A" last="Marabelle">A. Marabelle</name><affiliation wicri:level="1"><nlm:affiliation>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800</wicri:regionArea></affiliation></author><author><name sortKey="Michiels, S" sort="Michiels, S" uniqKey="Michiels S" first="S" last="Michiels">S. Michiels</name><affiliation wicri:level="1"><nlm:affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Gustave Roussy Cancer Campus, Villejuif, 94800</wicri:regionArea></affiliation></author><author><name sortKey="Cavalcanti, A" sort="Cavalcanti, A" uniqKey="Cavalcanti A" first="A" last="Cavalcanti">A. Cavalcanti</name><affiliation wicri:level="1"><nlm:affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Gustave Roussy Cancer Campus, Villejuif, 94800</wicri:regionArea></affiliation></author><author><name sortKey="Smyth, M J" sort="Smyth, M J" uniqKey="Smyth M" first="M J" last="Smyth">M J Smyth</name><affiliation wicri:level="1"><nlm:affiliation>Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006</wicri:regionArea></affiliation></author><author><name sortKey="Weber, J S" sort="Weber, J S" uniqKey="Weber J" first="J S" last="Weber">J S Weber</name><affiliation wicri:level="1"><nlm:affiliation>Laura & Isaac Perlmutter Cancer Center, New York University Medical Center, New York, NY, 10016, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laura & Isaac Perlmutter Cancer Center, New York University Medical Center, New York, NY, 10016</wicri:regionArea></affiliation></author><author><name sortKey="Eggermont, A M" sort="Eggermont, A M" uniqKey="Eggermont A" first="A M" last="Eggermont">A M Eggermont</name><affiliation wicri:level="1"><nlm:affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Gustave Roussy Cancer Campus, Villejuif, 94800</wicri:regionArea></affiliation></author><author><name sortKey="Zitvogel, L" sort="Zitvogel, L" uniqKey="Zitvogel L" first="L" last="Zitvogel">L. Zitvogel</name><affiliation wicri:level="1"><nlm:affiliation>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800, France. Laurence.ZITVOGEL@gustaveroussy.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:28928380</idno><idno type="pmid">28928380</idno><idno type="doi">10.1038/s41467-017-00608-2</idno><idno type="wicri:Area/PubMed/Corpus">000489</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000489</idno><idno type="wicri:Area/PubMed/Curation">000487</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000487</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Predictors of responses to immune checkpoint blockade in advanced melanoma.</title><author><name sortKey="Jacquelot, N" sort="Jacquelot, N" uniqKey="Jacquelot N" first="N" last="Jacquelot">N. Jacquelot</name><affiliation wicri:level="1"><nlm:affiliation>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800</wicri:regionArea></affiliation></author><author><name sortKey="Roberti, M P" sort="Roberti, M P" uniqKey="Roberti M" first="M P" last="Roberti">M P Roberti</name><affiliation wicri:level="1"><nlm:affiliation>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800</wicri:regionArea></affiliation></author><author><name sortKey="Enot, D P" sort="Enot, D P" uniqKey="Enot D" first="D P" last="Enot">D P Enot</name><affiliation wicri:level="1"><nlm:affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Gustave Roussy Cancer Campus, Villejuif, 94800</wicri:regionArea></affiliation></author><author><name sortKey="Rusakiewicz, S" sort="Rusakiewicz, S" uniqKey="Rusakiewicz S" first="S" last="Rusakiewicz">S. Rusakiewicz</name><affiliation wicri:level="1"><nlm:affiliation>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800</wicri:regionArea></affiliation></author><author><name sortKey="Ternes, N" sort="Ternes, N" uniqKey="Ternes N" first="N" last="Ternès">N. Ternès</name><affiliation wicri:level="1"><nlm:affiliation>University Paris-Saclay, Kremlin Bicêtre, 94 276, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>University Paris-Saclay, Kremlin Bicêtre, 94 276</wicri:regionArea></affiliation></author><author><name sortKey="Jegou, S" sort="Jegou, S" uniqKey="Jegou S" first="S" last="Jegou">S. Jegou</name><affiliation wicri:level="1"><nlm:affiliation>Saint Antoine Hospital, INSERM ERL 1157-CNRS UMR 7203, Paris, 75005, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Saint Antoine Hospital, INSERM ERL 1157-CNRS UMR 7203, Paris, 75005</wicri:regionArea></affiliation></author><author><name sortKey="Woods, D M" sort="Woods, D M" uniqKey="Woods D" first="D M" last="Woods">D M Woods</name><affiliation wicri:level="1"><nlm:affiliation>Laura & Isaac Perlmutter Cancer Center, New York University Medical Center, New York, NY, 10016, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laura & Isaac Perlmutter Cancer Center, New York University Medical Center, New York, NY, 10016</wicri:regionArea></affiliation></author><author><name sortKey="Sodre, A L" sort="Sodre, A L" uniqKey="Sodre A" first="A L" last="Sodré">A L Sodré</name><affiliation wicri:level="1"><nlm:affiliation>Laura & Isaac Perlmutter Cancer Center, New York University Medical Center, New York, NY, 10016, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laura & Isaac Perlmutter Cancer Center, New York University Medical Center, New York, NY, 10016</wicri:regionArea></affiliation></author><author><name sortKey="Hansen, M" sort="Hansen, M" uniqKey="Hansen M" first="M" last="Hansen">M. Hansen</name><affiliation wicri:level="1"><nlm:affiliation>Center for Cancer Immune Therapy, Department of Hematology and Oncology, Copenhagen University Hospital, Herlev, DK-2730, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Center for Cancer Immune Therapy, Department of Hematology and Oncology, Copenhagen University Hospital, Herlev, DK-2730</wicri:regionArea></affiliation></author><author><name sortKey="Meirow, Y" sort="Meirow, Y" uniqKey="Meirow Y" first="Y" last="Meirow">Y. Meirow</name><affiliation wicri:level="1"><nlm:affiliation>The Lautenberg Center for General and Tumor Immunology, BioMedical Research institute Israel Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, 91120, Israel.</nlm:affiliation><country xml:lang="fr">Israël</country><wicri:regionArea>The Lautenberg Center for General and Tumor Immunology, BioMedical Research institute Israel Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, 91120</wicri:regionArea></affiliation></author><author><name sortKey="Sade Feldman, M" sort="Sade Feldman, M" uniqKey="Sade Feldman M" first="M" last="Sade-Feldman">M. Sade-Feldman</name><affiliation wicri:level="1"><nlm:affiliation>The Lautenberg Center for General and Tumor Immunology, BioMedical Research institute Israel Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, 91120, Israel.</nlm:affiliation><country xml:lang="fr">Israël</country><wicri:regionArea>The Lautenberg Center for General and Tumor Immunology, BioMedical Research institute Israel Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, 91120</wicri:regionArea></affiliation></author><author><name sortKey="Burra, A" sort="Burra, A" uniqKey="Burra A" first="A" last="Burra">A. Burra</name><affiliation wicri:level="1"><nlm:affiliation>Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, CA, 94143, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, CA, 94143</wicri:regionArea></affiliation></author><author><name sortKey="Kwek, S S" sort="Kwek, S S" uniqKey="Kwek S" first="S S" last="Kwek">S S Kwek</name><affiliation wicri:level="1"><nlm:affiliation>Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, CA, 94143, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, CA, 94143</wicri:regionArea></affiliation></author><author><name sortKey="Flament, C" sort="Flament, C" uniqKey="Flament C" first="C" last="Flament">C. Flament</name><affiliation wicri:level="1"><nlm:affiliation>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800</wicri:regionArea></affiliation></author><author><name sortKey="Messaoudene, M" sort="Messaoudene, M" uniqKey="Messaoudene M" first="M" last="Messaoudene">M. Messaoudene</name><affiliation wicri:level="1"><nlm:affiliation>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800</wicri:regionArea></affiliation></author><author><name sortKey="Duong, C P M" sort="Duong, C P M" uniqKey="Duong C" first="C P M" last="Duong">C P M. Duong</name><affiliation wicri:level="1"><nlm:affiliation>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800</wicri:regionArea></affiliation></author><author><name sortKey="Chen, L" sort="Chen, L" uniqKey="Chen L" first="L" last="Chen">L. Chen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Immunobiology, Yale School of Medicine, 10 Amistad Street, New Haven, CT, 06519, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Immunobiology, Yale School of Medicine, 10 Amistad Street, New Haven, CT, 06519</wicri:regionArea></affiliation></author><author><name sortKey="Kwon, B S" sort="Kwon, B S" uniqKey="Kwon B" first="B S" last="Kwon">B S Kwon</name><affiliation wicri:level="1"><nlm:affiliation>Eutilex, Suite# 1401 Daeryung Technotown 17 Gasan Digital 1-ro 25, Geumcheon-gu, Seoul, 08594, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Eutilex, Suite# 1401 Daeryung Technotown 17 Gasan Digital 1-ro 25, Geumcheon-gu, Seoul, 08594</wicri:regionArea></affiliation></author><author><name sortKey="Anderson, A C" sort="Anderson, A C" uniqKey="Anderson A" first="A C" last="Anderson">A C Anderson</name><affiliation wicri:level="1"><nlm:affiliation>Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115</wicri:regionArea></affiliation></author><author><name sortKey="Kuchroo, V K" sort="Kuchroo, V K" uniqKey="Kuchroo V" first="V K" last="Kuchroo">V K Kuchroo</name><affiliation wicri:level="1"><nlm:affiliation>Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115</wicri:regionArea></affiliation></author><author><name sortKey="Weide, B" sort="Weide, B" uniqKey="Weide B" first="B" last="Weide">B. Weide</name><affiliation wicri:level="1"><nlm:affiliation>Department of Dermatology, University Medical Center Tübingen, Tübingen, 72076, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, University Medical Center Tübingen, Tübingen, 72076</wicri:regionArea></affiliation></author><author><name sortKey="Aubin, F" sort="Aubin, F" uniqKey="Aubin F" first="F" last="Aubin">F. Aubin</name><affiliation wicri:level="1"><nlm:affiliation>Université de Franche Comté, EA3181, SFR4234, Service de Dermatologie, Centre Hospitalier Universitaire (CHU), Besançon, 25000, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Franche Comté, EA3181, SFR4234, Service de Dermatologie, Centre Hospitalier Universitaire (CHU), Besançon, 25000</wicri:regionArea></affiliation></author><author><name sortKey="Borg, C" sort="Borg, C" uniqKey="Borg C" first="C" last="Borg">C. Borg</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Oncology, University Hospital of Besancon, 3 Boulevard Alexander Fleming, Besancon, F-25030, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Medical Oncology, University Hospital of Besancon, 3 Boulevard Alexander Fleming, Besancon, F-25030</wicri:regionArea></affiliation></author><author><name sortKey="Dalle, S" sort="Dalle, S" uniqKey="Dalle S" first="S" last="Dalle">S. Dalle</name><affiliation wicri:level="1"><nlm:affiliation>Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon and University Claude Bernard Lyon 1, Lyon, 69000, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon and University Claude Bernard Lyon 1, Lyon, 69000</wicri:regionArea></affiliation></author><author><name sortKey="Beatrix, O" sort="Beatrix, O" uniqKey="Beatrix O" first="O" last="Beatrix">O. Beatrix</name><affiliation wicri:level="1"><nlm:affiliation>Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon and University Claude Bernard Lyon 1, Lyon, 69000, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon and University Claude Bernard Lyon 1, Lyon, 69000</wicri:regionArea></affiliation></author><author><name sortKey="Ayyoub, M" sort="Ayyoub, M" uniqKey="Ayyoub M" first="M" last="Ayyoub">M. Ayyoub</name><affiliation wicri:level="1"><nlm:affiliation>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800</wicri:regionArea></affiliation></author><author><name sortKey="Balme, B" sort="Balme, B" uniqKey="Balme B" first="B" last="Balme">B. Balme</name><affiliation wicri:level="1"><nlm:affiliation>Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon and University Claude Bernard Lyon 1, Lyon, 69000, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon and University Claude Bernard Lyon 1, Lyon, 69000</wicri:regionArea></affiliation></author><author><name sortKey="Tomasic, G" sort="Tomasic, G" uniqKey="Tomasic G" first="G" last="Tomasic">G. Tomasic</name><affiliation wicri:level="1"><nlm:affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Gustave Roussy Cancer Campus, Villejuif, 94800</wicri:regionArea></affiliation></author><author><name sortKey="Di Giacomo, A M" sort="Di Giacomo, A M" uniqKey="Di Giacomo A" first="A M" last="Di Giacomo">A M Di Giacomo</name><affiliation wicri:level="1"><nlm:affiliation>Medical Oncology and Immunotherapy Division, University Hospital of Siena, Viale Bracci, 14, Siena, 53100, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Medical Oncology and Immunotherapy Division, University Hospital of Siena, Viale Bracci, 14, Siena, 53100</wicri:regionArea></affiliation></author><author><name sortKey="Maio, M" sort="Maio, M" uniqKey="Maio M" first="M" last="Maio">M. Maio</name><affiliation wicri:level="1"><nlm:affiliation>Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Instituto Toscano Tumori, Siena, 53100, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Instituto Toscano Tumori, Siena, 53100</wicri:regionArea></affiliation></author><author><name sortKey="Schadendorf, D" sort="Schadendorf, D" uniqKey="Schadendorf D" first="D" last="Schadendorf">D. Schadendorf</name><affiliation wicri:level="1"><nlm:affiliation>Department of Dermatology, University Hospital, University Duisburg-Essen, Essen, Germany & German Cancer Consortium (DKTZ), Heidelberg, D-69120, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, University Hospital, University Duisburg-Essen, Essen, Germany & German Cancer Consortium (DKTZ), Heidelberg, D-69120</wicri:regionArea></affiliation></author><author><name sortKey="Melero, I" sort="Melero, I" uniqKey="Melero I" first="I" last="Melero">I. Melero</name><affiliation wicri:level="1"><nlm:affiliation>Division of Gene Therapy and Hepatology, Centre for Applied Medical Research, Pamplona, 31008, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Division of Gene Therapy and Hepatology, Centre for Applied Medical Research, Pamplona, 31008</wicri:regionArea></affiliation></author><author><name sortKey="Dreno, B" sort="Dreno, B" uniqKey="Dreno B" first="B" last="Dréno">B. Dréno</name><affiliation wicri:level="1"><nlm:affiliation>Department of Onco-dermatology, CIC Biotherapy, INSERM U1232, CHU Nantes, Nantes, 44000, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Onco-dermatology, CIC Biotherapy, INSERM U1232, CHU Nantes, Nantes, 44000</wicri:regionArea></affiliation></author><author><name sortKey="Khammari, A" sort="Khammari, A" uniqKey="Khammari A" first="A" last="Khammari">A. Khammari</name><affiliation wicri:level="1"><nlm:affiliation>Department of Onco-dermatology, CIC Biotherapy, INSERM U1232, CHU Nantes, Nantes, 44000, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Onco-dermatology, CIC Biotherapy, INSERM U1232, CHU Nantes, Nantes, 44000</wicri:regionArea></affiliation></author><author><name sortKey="Dummer, R" sort="Dummer, R" uniqKey="Dummer R" first="R" last="Dummer">R. Dummer</name><affiliation wicri:level="1"><nlm:affiliation>Department of Dermatology, University Hospital Zürich and University of Zürich, Zürich, 8091, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Dermatology, University Hospital Zürich and University of Zürich, Zürich, 8091</wicri:regionArea></affiliation></author><author><name sortKey="Levesque, M" sort="Levesque, M" uniqKey="Levesque M" first="M" last="Levesque">M. Levesque</name><affiliation wicri:level="1"><nlm:affiliation>Department of Dermatology, University Hospital Zürich and University of Zürich, Zürich, 8091, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Dermatology, University Hospital Zürich and University of Zürich, Zürich, 8091</wicri:regionArea></affiliation></author><author><name sortKey="Koguchi, Y" sort="Koguchi, Y" uniqKey="Koguchi Y" first="Y" last="Koguchi">Y. Koguchi</name><affiliation wicri:level="1"><nlm:affiliation>Earle A. Chiles Research Institute, Providence Cancer Center, Portland, OR, 97213, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Earle A. Chiles Research Institute, Providence Cancer Center, Portland, OR, 97213</wicri:regionArea></affiliation></author><author><name sortKey="Fong, L" sort="Fong, L" uniqKey="Fong L" first="L" last="Fong">L. Fong</name><affiliation wicri:level="1"><nlm:affiliation>Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, CA, 94143, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, CA, 94143</wicri:regionArea></affiliation></author><author><name sortKey="Lotem, M" sort="Lotem, M" uniqKey="Lotem M" first="M" last="Lotem">M. Lotem</name><affiliation wicri:level="1"><nlm:affiliation>Sharett Institute of Oncology, Hadassah Medical Organization, Jerusalem, 91120, Israel.</nlm:affiliation><country xml:lang="fr">Israël</country><wicri:regionArea>Sharett Institute of Oncology, Hadassah Medical Organization, Jerusalem, 91120</wicri:regionArea></affiliation></author><author><name sortKey="Baniyash, M" sort="Baniyash, M" uniqKey="Baniyash M" first="M" last="Baniyash">M. Baniyash</name><affiliation wicri:level="1"><nlm:affiliation>The Lautenberg Center for General and Tumor Immunology, BioMedical Research institute Israel Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, 91120, Israel.</nlm:affiliation><country xml:lang="fr">Israël</country><wicri:regionArea>The Lautenberg Center for General and Tumor Immunology, BioMedical Research institute Israel Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, 91120</wicri:regionArea></affiliation></author><author><name sortKey="Schmidt, H" sort="Schmidt, H" uniqKey="Schmidt H" first="H" last="Schmidt">H. Schmidt</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, Aarhus University Hospital, Aarhus, DK-8200, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Department of Oncology, Aarhus University Hospital, Aarhus, DK-8200</wicri:regionArea></affiliation></author><author><name sortKey="Svane, I M" sort="Svane, I M" uniqKey="Svane I" first="I M" last="Svane">I M Svane</name><affiliation wicri:level="1"><nlm:affiliation>Center for Cancer Immune Therapy, Department of Hematology and Oncology, Copenhagen University Hospital, Herlev, DK-2730, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Center for Cancer Immune Therapy, Department of Hematology and Oncology, Copenhagen University Hospital, Herlev, DK-2730</wicri:regionArea></affiliation></author><author><name sortKey="Kroemer, G" sort="Kroemer, G" uniqKey="Kroemer G" first="G" last="Kroemer">G. Kroemer</name><affiliation wicri:level="1"><nlm:affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Gustave Roussy Cancer Campus, Villejuif, 94800</wicri:regionArea></affiliation></author><author><name sortKey="Marabelle, A" sort="Marabelle, A" uniqKey="Marabelle A" first="A" last="Marabelle">A. Marabelle</name><affiliation wicri:level="1"><nlm:affiliation>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800</wicri:regionArea></affiliation></author><author><name sortKey="Michiels, S" sort="Michiels, S" uniqKey="Michiels S" first="S" last="Michiels">S. Michiels</name><affiliation wicri:level="1"><nlm:affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Gustave Roussy Cancer Campus, Villejuif, 94800</wicri:regionArea></affiliation></author><author><name sortKey="Cavalcanti, A" sort="Cavalcanti, A" uniqKey="Cavalcanti A" first="A" last="Cavalcanti">A. Cavalcanti</name><affiliation wicri:level="1"><nlm:affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Gustave Roussy Cancer Campus, Villejuif, 94800</wicri:regionArea></affiliation></author><author><name sortKey="Smyth, M J" sort="Smyth, M J" uniqKey="Smyth M" first="M J" last="Smyth">M J Smyth</name><affiliation wicri:level="1"><nlm:affiliation>Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006</wicri:regionArea></affiliation></author><author><name sortKey="Weber, J S" sort="Weber, J S" uniqKey="Weber J" first="J S" last="Weber">J S Weber</name><affiliation wicri:level="1"><nlm:affiliation>Laura & Isaac Perlmutter Cancer Center, New York University Medical Center, New York, NY, 10016, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laura & Isaac Perlmutter Cancer Center, New York University Medical Center, New York, NY, 10016</wicri:regionArea></affiliation></author><author><name sortKey="Eggermont, A M" sort="Eggermont, A M" uniqKey="Eggermont A" first="A M" last="Eggermont">A M Eggermont</name><affiliation wicri:level="1"><nlm:affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Gustave Roussy Cancer Campus, Villejuif, 94800</wicri:regionArea></affiliation></author><author><name sortKey="Zitvogel, L" sort="Zitvogel, L" uniqKey="Zitvogel L" first="L" last="Zitvogel">L. Zitvogel</name><affiliation wicri:level="1"><nlm:affiliation>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800, France. Laurence.ZITVOGEL@gustaveroussy.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800</wicri:regionArea></affiliation></author></analytic><series><title level="j">Nature communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we retrospectively observed, in eight cohorts enrolling 190 MMel patients treated with ipilimumab, that PD-L1 expression on peripheral T cells was prognostic on overall and progression-free survival. Moreover, detectable CD137 on circulating CD8(+) T cells was associated with the disease-free status of resected stage III MMel patients after adjuvant ipilimumab + nivolumab (but not nivolumab alone). These biomarkers should be validated in prospective trials in MMel.The clinical management of metastatic melanoma requires predictors of the response to checkpoint blockade. Here, the authors use immunological assays to identify potential prognostic/predictive biomarkers in circulating blood cells and in tumor-infiltrating lymphocytes from patients with resected stage III melanoma.</div></front></TEI><pubmed><MedlineCitation Status="In-Data-Review" Owner="NLM"><PMID Version="1">28928380</PMID><DateCreated><Year>2017</Year><Month>09</Month><Day>20</Day></DateCreated><DateRevised><Year>2017</Year><Month>09</Month><Day>24</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2041-1723</ISSN><JournalIssue CitedMedium="Internet"><Volume>8</Volume><Issue>1</Issue><PubDate><Year>2017</Year><Month>Sep</Month><Day>19</Day></PubDate></JournalIssue><Title>Nature communications</Title><ISOAbbreviation>Nat Commun</ISOAbbreviation></Journal><ArticleTitle>Predictors of responses to immune checkpoint blockade in advanced melanoma.</ArticleTitle><Pagination><MedlinePgn>592</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/s41467-017-00608-2</ELocationID><Abstract><AbstractText>Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we retrospectively observed, in eight cohorts enrolling 190 MMel patients treated with ipilimumab, that PD-L1 expression on peripheral T cells was prognostic on overall and progression-free survival. Moreover, detectable CD137 on circulating CD8(+) T cells was associated with the disease-free status of resected stage III MMel patients after adjuvant ipilimumab + nivolumab (but not nivolumab alone). These biomarkers should be validated in prospective trials in MMel.The clinical management of metastatic melanoma requires predictors of the response to checkpoint blockade. Here, the authors use immunological assays to identify potential prognostic/predictive biomarkers in circulating blood cells and in tumor-infiltrating lymphocytes from patients with resected stage III melanoma.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Jacquelot</LastName><ForeName>N</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>University Paris-Saclay, Kremlin Bicêtre, 94 276, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Roberti</LastName><ForeName>M P</ForeName><Initials>MP</Initials><AffiliationInfo><Affiliation>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Enot</LastName><ForeName>D P</ForeName><Initials>DP</Initials><AffiliationInfo><Affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rusakiewicz</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>CIC1428, Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ternès</LastName><ForeName>N</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>University Paris-Saclay, Kremlin Bicêtre, 94 276, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Gustave Roussy, Université Paris-Saclay, Service de Biostatistique et d'Epidémiologie, Villejuif, F-94805, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jegou</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Saint Antoine Hospital, INSERM ERL 1157-CNRS UMR 7203, Paris, 75005, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Woods</LastName><ForeName>D M</ForeName><Initials>DM</Initials><AffiliationInfo><Affiliation>Laura & Isaac Perlmutter Cancer Center, New York University Medical Center, New York, NY, 10016, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sodré</LastName><ForeName>A L</ForeName><Initials>AL</Initials><AffiliationInfo><Affiliation>Laura & Isaac Perlmutter Cancer Center, New York University Medical Center, New York, NY, 10016, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hansen</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Center for Cancer Immune Therapy, Department of Hematology and Oncology, Copenhagen University Hospital, Herlev, DK-2730, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Meirow</LastName><ForeName>Y</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>The Lautenberg Center for General and Tumor Immunology, BioMedical Research institute Israel Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, 91120, Israel.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sade-Feldman</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>The Lautenberg Center for General and Tumor Immunology, BioMedical Research institute Israel Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, 91120, Israel.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Burra</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, CA, 94143, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kwek</LastName><ForeName>S S</ForeName><Initials>SS</Initials><AffiliationInfo><Affiliation>Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, CA, 94143, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Flament</LastName><ForeName>C</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>University Paris-Saclay, Kremlin Bicêtre, 94 276, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>CIC1428, Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Messaoudene</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Duong</LastName><ForeName>C P M</ForeName><Initials>CPM</Initials><AffiliationInfo><Affiliation>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>L</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Immunobiology, Yale School of Medicine, 10 Amistad Street, New Haven, CT, 06519, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kwon</LastName><ForeName>B S</ForeName><Initials>BS</Initials><AffiliationInfo><Affiliation>Eutilex, Suite# 1401 Daeryung Technotown 17 Gasan Digital 1-ro 25, Geumcheon-gu, Seoul, 08594, Korea.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Section of Clinical Immunology, Allergy, and Rheumatology, Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA, 70112, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Anderson</LastName><ForeName>A C</ForeName><Initials>AC</Initials><AffiliationInfo><Affiliation>Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kuchroo</LastName><ForeName>V K</ForeName><Initials>VK</Initials><AffiliationInfo><Affiliation>Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Weide</LastName><ForeName>B</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Dermatology, University Medical Center Tübingen, Tübingen, 72076, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Aubin</LastName><ForeName>F</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Université de Franche Comté, EA3181, SFR4234, Service de Dermatologie, Centre Hospitalier Universitaire (CHU), Besançon, 25000, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Borg</LastName><ForeName>C</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Medical Oncology, University Hospital of Besancon, 3 Boulevard Alexander Fleming, Besancon, F-25030, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Clinical Investigational Centre, CIC-1431, University Hospital of Besançon, Besançon, 25030, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>INSERM U1098, University of Franche-Comté, Besançon, 25020, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dalle</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon and University Claude Bernard Lyon 1, Lyon, 69000, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Centre de Recherche en Cancérologie de Lyon, Lyon, 69000, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Beatrix</LastName><ForeName>O</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon and University Claude Bernard Lyon 1, Lyon, 69000, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ayyoub</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Balme</LastName><ForeName>B</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon and University Claude Bernard Lyon 1, Lyon, 69000, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Pathology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Lyon, 69000, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tomasic</LastName><ForeName>G</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Pathology, Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Di Giacomo</LastName><ForeName>A M</ForeName><Initials>AM</Initials><AffiliationInfo><Affiliation>Medical Oncology and Immunotherapy Division, University Hospital of Siena, Viale Bracci, 14, Siena, 53100, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Maio</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Instituto Toscano Tumori, Siena, 53100, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schadendorf</LastName><ForeName>D</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Dermatology, University Hospital, University Duisburg-Essen, Essen, Germany & German Cancer Consortium (DKTZ), Heidelberg, D-69120, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Melero</LastName><ForeName>I</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Division of Gene Therapy and Hepatology, Centre for Applied Medical Research, Pamplona, 31008, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Oncology Department, University Clinic of Navarra, Pamplona, 31008, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Centro de Investigación cBiomedica en Red de Oncologia, Pamplona, 31008, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dréno</LastName><ForeName>B</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Onco-dermatology, CIC Biotherapy, INSERM U1232, CHU Nantes, Nantes, 44000, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Khammari</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Onco-dermatology, CIC Biotherapy, INSERM U1232, CHU Nantes, Nantes, 44000, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dummer</LastName><ForeName>R</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Dermatology, University Hospital Zürich and University of Zürich, Zürich, 8091, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Levesque</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Dermatology, University Hospital Zürich and University of Zürich, Zürich, 8091, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Koguchi</LastName><ForeName>Y</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Earle A. Chiles Research Institute, Providence Cancer Center, Portland, OR, 97213, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fong</LastName><ForeName>L</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, CA, 94143, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lotem</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Sharett Institute of Oncology, Hadassah Medical Organization, Jerusalem, 91120, Israel.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Baniyash</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>The Lautenberg Center for General and Tumor Immunology, BioMedical Research institute Israel Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, 91120, Israel.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schmidt</LastName><ForeName>H</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Oncology, Aarhus University Hospital, Aarhus, DK-8200, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Svane</LastName><ForeName>I M</ForeName><Initials>IM</Initials><AffiliationInfo><Affiliation>Center for Cancer Immune Therapy, Department of Hematology and Oncology, Copenhagen University Hospital, Herlev, DK-2730, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kroemer</LastName><ForeName>G</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>INSERM U1138, Centre de Recherche des Cordeliers, Paris, 75006, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, 75006, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université Paris Descartes, Sorbonne Paris Cité, Paris, 75006, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université Pierre et Marie Curie, Paris, 75005, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, 75015, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Marabelle</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>CIC1428, Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Michiels</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Gustave Roussy, Université Paris-Saclay, Service de Biostatistique et d'Epidémiologie, Villejuif, F-94805, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cavalcanti</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Surgery, Gustave Roussy Cancer Center, Villejuif, 94800, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Dermatology, Gustave Roussy Cancer Center, Villejuif, 94800, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Smyth</LastName><ForeName>M J</ForeName><Initials>MJ</Initials><Identifier Source="ORCID">http://orcid.org/0000-0001-7098-7240</Identifier><AffiliationInfo><Affiliation>Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>School of Medicine, University of Queensland, Herston, QLD, 4006, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Weber</LastName><ForeName>J S</ForeName><Initials>JS</Initials><AffiliationInfo><Affiliation>Laura & Isaac Perlmutter Cancer Center, New York University Medical Center, New York, NY, 10016, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Eggermont</LastName><ForeName>A M</ForeName><Initials>AM</Initials><AffiliationInfo><Affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zitvogel</LastName><ForeName>L</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, 94800, France. Laurence.ZITVOGEL@gustaveroussy.fr.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>University Paris-Saclay, Kremlin Bicêtre, 94 276, France. Laurence.ZITVOGEL@gustaveroussy.fr.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Gustave Roussy Cancer Campus, Villejuif, 94800, France. Laurence.ZITVOGEL@gustaveroussy.fr.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>CIC1428, Gustave Roussy Cancer Campus, Villejuif, 94800, France. Laurence.ZITVOGEL@gustaveroussy.fr.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Gustave Roussy, Université Paris-Saclay, Service de Biostatistique et d'Epidémiologie, Villejuif, F-94805, France. Laurence.ZITVOGEL@gustaveroussy.fr.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>09</Month><Day>19</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Nat Commun</MedlineTA><NlmUniqueID>101528555</NlmUniqueID><ISSNLinking>2041-1723</ISSNLinking></MedlineJournalInfo><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>J Clin Invest. 2016 Jan;126(1):318-34</RefSource><PMID Version="1">26657860</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Cancer Cell. 2015 Apr 13;27(4):450-61</RefSource><PMID Version="1">25858804</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Int J Cancer. 2005 Nov 20;117(4):596-604</RefSource><PMID 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