Predictors of responses to immune checkpoint blockade in advanced melanoma
Identifieur interne : 000568 ( Main/Exploration ); précédent : 000567; suivant : 000569Predictors 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 ; 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, États-Unis] ; 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 ; I. M. Svane ; G. Kroemer [France] ; A. Marabelle [France] ; S. Michiels [France] ; A. Cavalcanti [France] ; M. J. Smyth ; 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.
Url:
DOI: 10.1038/s41467-017-00608-2
PubMed: 28928380
PubMed Central: 5605517
Affiliations:
- Allemagne, Corée du Sud, Espagne, France, Israël, Italie, Suisse, États-Unis
- Auvergne-Rhône-Alpes, Bade-Wurtemberg, Bourgogne-Franche-Comté, Californie, Connecticut, District de Karlsruhe, District de Tübingen, Franche-Comté, Louisiane, Massachusetts, Oregon, Pays de la Loire, Rhône-Alpes, Région capitale de Séoul, État de New York, Île-de-France
- Besançon, France, Heidelberg, Lyon, Nantes, Paris, Séoul, Tübingen
- Université de Franche-Comté
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Aubin</name><affiliation wicri:level="4"><nlm:aff id="Aff17">Université de Franche Comté, EA3181, SFR4234, Service de Dermatologie, Centre Hospitalier Universitaire (CHU), Besançon, 25000 France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Université de Franche Comté, EA3181, SFR4234, Service de Dermatologie, Centre Hospitalier Universitaire (CHU), Besançon</wicri:regionArea><placeName><region type="region">Bourgogne-Franche-Comté</region><region type="old region">Franche-Comté</region><settlement type="city">Besançon</settlement><settlement type="city" wicri:auto="siege">Besançon</settlement></placeName><orgName type="university">Université de Franche-Comté</orgName></affiliation></author><author><name sortKey="Borg, C" sort="Borg, C" uniqKey="Borg C" first="C." last="Borg">C. 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Dalle</name><affiliation wicri:level="3"><nlm:aff id="Aff21">Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon and University Claude Bernard Lyon 1, Lyon, 69000 France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon and University Claude Bernard Lyon 1, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff22"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0384 0005</institution-id><institution-id institution-id-type="GRID">grid.462282.8</institution-id><institution>Centre de Recherche en Cancérologie de Lyon,</institution></institution-wrap>Lyon, 69000 France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Lyon</wicri:regionArea></affiliation></author><author><name sortKey="Beatrix, O" sort="Beatrix, O" uniqKey="Beatrix O" first="O." last="Beatrix">O. 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Weide</name><affiliation wicri:level="3"><nlm:aff id="Aff16">Department of Dermatology, University Medical Center Tübingen, Tübingen, 72076 Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, University Medical Center Tübingen, Tübingen</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Tübingen</settlement></placeName></affiliation></author><author><name sortKey="Aubin, F" sort="Aubin, F" uniqKey="Aubin F" first="F." last="Aubin">F. 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M." last="Di Giacomo">A. M. Di Giacomo</name><affiliation wicri:level="1"><nlm:aff id="Aff25"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1759 0844</institution-id><institution-id institution-id-type="GRID">grid.411477.0</institution-id><institution>Medical Oncology and Immunotherapy Division,</institution><institution>University Hospital of Siena,</institution></institution-wrap>Viale Bracci, 14, Siena, 53100 Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Viale Bracci, 14, Siena</wicri:regionArea><wicri:noRegion>Siena</wicri:noRegion></affiliation></author><author><name sortKey="Maio, M" sort="Maio, M" uniqKey="Maio M" first="M." last="Maio">M. 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Melero</name><affiliation wicri:level="1"><nlm:aff id="Aff28">Division of Gene Therapy and Hepatology, Centre for Applied Medical Research, Pamplona, 31008 Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Division of Gene Therapy and Hepatology, Centre for Applied Medical Research, Pamplona</wicri:regionArea><wicri:noRegion>Pamplona</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff29"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2191 685X</institution-id><institution-id institution-id-type="GRID">grid.411730.0</institution-id><institution>Oncology Department,</institution><institution>University Clinic of Navarra,</institution></institution-wrap>Pamplona, 31008 Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Pamplona</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff30">Centro de Investigación cBiomedica en Red de Oncologia, Pamplona, 31008 Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Centro de Investigación cBiomedica en Red de Oncologia, Pamplona</wicri:regionArea><wicri:noRegion>Pamplona</wicri:noRegion></affiliation></author><author><name sortKey="Dreno, B" sort="Dreno, B" uniqKey="Dreno B" first="B." last="Dréno">B. Dréno</name><affiliation wicri:level="3"><nlm:aff id="Aff31"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0450 4986</institution-id><institution-id institution-id-type="GRID">grid.429536.f</institution-id><institution>Department of Onco-dermatology,</institution><institution>CIC Biotherapy,</institution></institution-wrap>INSERM U1232, CHU Nantes, Nantes, 44000 France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1232, CHU Nantes, Nantes</wicri:regionArea><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Khammari, A" sort="Khammari, A" uniqKey="Khammari A" first="A." last="Khammari">A. 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Dummer</name><affiliation wicri:level="1"><nlm:aff id="Aff32"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0478 9977</institution-id><institution-id institution-id-type="GRID">grid.412004.3</institution-id><institution>Department of Dermatology,</institution><institution>University Hospital Zürich and University of Zürich,</institution></institution-wrap>Zürich, 8091 Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Zürich</wicri:regionArea></affiliation></author><author><name sortKey="Levesque, M" sort="Levesque, M" uniqKey="Levesque M" first="M." last="Levesque">M. 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Chiles Research Institute, Providence Cancer Center, Portland</wicri:cityArea></affiliation></author><author><name sortKey="Fong, L" sort="Fong, L" uniqKey="Fong L" first="L." last="Fong">L. Fong</name><affiliation wicri:level="2"><nlm:aff id="Aff11"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2297 6811</institution-id><institution-id institution-id-type="GRID">grid.266102.1</institution-id><institution>Division of Hematology/Oncology, Department of Medicine,</institution><institution>University of California,</institution></institution-wrap>San Francisco, CA 94143 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>San Francisco</wicri:cityArea></affiliation></author><author><name sortKey="Lotem, M" sort="Lotem, M" uniqKey="Lotem M" first="M." last="Lotem">M. 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Marabelle</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2284 9388</institution-id><institution-id institution-id-type="GRID">grid.14925.3b</institution-id><institution>INSERM U1015,</institution><institution>Gustave Roussy Cancer Campus,</institution></institution-wrap>Villejuif, 94800 France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Villejuif</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2284 9388</institution-id><institution-id institution-id-type="GRID">grid.14925.3b</institution-id><institution>Gustave Roussy Cancer Campus,</institution></institution-wrap>Villejuif, 94800 France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Villejuif</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2284 9388</institution-id><institution-id institution-id-type="GRID">grid.14925.3b</institution-id><institution>CIC1428,</institution><institution>Gustave Roussy Cancer Campus,</institution></institution-wrap>Villejuif, 94800 France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Villejuif</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:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2284 9388</institution-id><institution-id institution-id-type="GRID">grid.14925.3b</institution-id><institution>Gustave Roussy Cancer Campus,</institution></institution-wrap>Villejuif, 94800 France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Villejuif</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 4910 6535</institution-id><institution-id institution-id-type="GRID">grid.460789.4</institution-id><institution>Gustave Roussy,</institution><institution>Université Paris-Saclay, Service de Biostatistique et d’Epidémiologie,</institution></institution-wrap>Villejuif, F-94805 France</nlm:aff><country wicri:rule="zip">France</country><wicri:regionArea>Villejuif, F-94805 France</wicri:regionArea><wicri:noRegion>94805 France</wicri:noRegion><wicri:noRegion>94805 France</wicri:noRegion></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:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2284 9388</institution-id><institution-id institution-id-type="GRID">grid.14925.3b</institution-id><institution>Gustave Roussy Cancer Campus,</institution></institution-wrap>Villejuif, 94800 France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Villejuif</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff41"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2284 9388</institution-id><institution-id institution-id-type="GRID">grid.14925.3b</institution-id><institution>Department of Surgery,</institution><institution>Gustave Roussy Cancer Center,</institution></institution-wrap>Villejuif, 94800 France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Villejuif</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff42"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2284 9388</institution-id><institution-id institution-id-type="GRID">grid.14925.3b</institution-id><institution>Department of Dermatology,</institution><institution>Gustave Roussy Cancer Center,</institution></institution-wrap>Villejuif, 94800 France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Villejuif</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><nlm:aff id="Aff43"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2294 1395</institution-id><institution-id institution-id-type="GRID">grid.1049.c</institution-id><institution>Immunology in Cancer and Infection Laboratory,</institution><institution>QIMR Berghofer Medical Research Institute,</institution></institution-wrap>Herston, QLD 4006 Australia</nlm:aff><wicri:noCountry code="subfield">QLD 4006 Australia</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff44"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9320 7537</institution-id><institution-id institution-id-type="GRID">grid.1003.2</institution-id><institution>School of Medicine,</institution><institution>University of Queensland,</institution></institution-wrap>Herston, QLD 4006 Australia</nlm:aff><wicri:noCountry code="subfield">QLD 4006 Australia</wicri:noCountry></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="2"><nlm:aff id="Aff8"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2109 4251</institution-id><institution-id institution-id-type="GRID">grid.240324.3</institution-id><institution>Laura & Isaac Perlmutter Cancer Center,</institution><institution>New York University Medical Center,</institution></institution-wrap>New York, NY 10016 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>New York</wicri:cityArea></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:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2284 9388</institution-id><institution-id institution-id-type="GRID">grid.14925.3b</institution-id><institution>Gustave Roussy Cancer Campus,</institution></institution-wrap>Villejuif, 94800 France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Villejuif</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:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2284 9388</institution-id><institution-id institution-id-type="GRID">grid.14925.3b</institution-id><institution>INSERM U1015,</institution><institution>Gustave Roussy Cancer Campus,</institution></institution-wrap>Villejuif, 94800 France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Villejuif</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 4910 6535</institution-id><institution-id institution-id-type="GRID">grid.460789.4</institution-id><institution>University Paris-Saclay,</institution></institution-wrap>Kremlin Bicêtre, 94 276 France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Kremlin Bicêtre</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2284 9388</institution-id><institution-id institution-id-type="GRID">grid.14925.3b</institution-id><institution>Gustave Roussy Cancer Campus,</institution></institution-wrap>Villejuif, 94800 France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Villejuif</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2284 9388</institution-id><institution-id institution-id-type="GRID">grid.14925.3b</institution-id><institution>CIC1428,</institution><institution>Gustave Roussy Cancer Campus,</institution></institution-wrap>Villejuif, 94800 France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Villejuif</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 4910 6535</institution-id><institution-id institution-id-type="GRID">grid.460789.4</institution-id><institution>Gustave Roussy,</institution><institution>Université Paris-Saclay, Service de Biostatistique et d’Epidémiologie,</institution></institution-wrap>Villejuif, F-94805 France</nlm:aff><country wicri:rule="zip">France</country><wicri:regionArea>Villejuif, F-94805 France</wicri:regionArea><wicri:noRegion>94805 France</wicri:noRegion><wicri:noRegion>94805 France</wicri:noRegion></affiliation></author></analytic><series><title level="j">Nature Communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">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<sup>+</sup> 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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Tartour, E" uniqKey="Tartour E">E Tartour</name></author><author><name sortKey="Zitvogel, L" uniqKey="Zitvogel L">L Zitvogel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sathyanarayanan, V" uniqKey="Sathyanarayanan V">V Sathyanarayanan</name></author><author><name sortKey="Neelapu, Ss" uniqKey="Neelapu S">SS Neelapu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kantoff, Pw" uniqKey="Kantoff P">PW Kantoff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rosenberg, Sa" uniqKey="Rosenberg S">SA Rosenberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="June, Ch" uniqKey="June C">CH June</name></author><author><name sortKey="Riddell, Sr" uniqKey="Riddell S">SR 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Jr" uniqKey="Brahmer J">JR Brahmer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Garon, Eb" uniqKey="Garon E">EB Garon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kleffel, S" uniqKey="Kleffel S">S Kleffel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ladoire, S" uniqKey="Ladoire S">S Ladoire</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Holmgaard, Rb" uniqKey="Holmgaard R">RB Holmgaard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kridel, R" uniqKey="Kridel R">R Kridel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Denkert, C" uniqKey="Denkert C">C Denkert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eggermont, Amm" uniqKey="Eggermont A">AMM Eggermont</name></author><author><name sortKey="Spatz, A" uniqKey="Spatz A">A Spatz</name></author><author><name sortKey="Robert, C" uniqKey="Robert C">C Robert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jacquelot, N" uniqKey="Jacquelot N">N Jacquelot</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jacquelot, N" uniqKey="Jacquelot N">N Jacquelot</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eggermont, Amm" uniqKey="Eggermont A">AMM Eggermont</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eggermont, Amm" uniqKey="Eggermont A">AMM Eggermont</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wolchok, Jd" uniqKey="Wolchok J">JD Wolchok</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hoos, A" uniqKey="Hoos A">A Hoos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hoos, A" uniqKey="Hoos A">A Hoos</name></author><author><name sortKey="Wolchok, Jd" uniqKey="Wolchok J">JD Wolchok</name></author><author><name sortKey="Humphrey, Rw" uniqKey="Humphrey R">RW Humphrey</name></author><author><name sortKey="Hodi, Fs" uniqKey="Hodi F">FS Hodi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Larkin, J" uniqKey="Larkin J">J Larkin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weide, B" uniqKey="Weide B">B Weide</name></author><author><name sortKey="Di Giacomo, Am" uniqKey="Di Giacomo A">AM Di Giacomo</name></author><author><name sortKey="Fonsatti, E" uniqKey="Fonsatti E">E Fonsatti</name></author><author><name sortKey="Zitvogel, L" uniqKey="Zitvogel L">L Zitvogel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ascierto, Pa" uniqKey="Ascierto P">PA Ascierto</name></author><author><name sortKey="Simeone, E" uniqKey="Simeone E">E Simeone</name></author><author><name sortKey="Sznol, M" uniqKey="Sznol M">M Sznol</name></author><author><name sortKey="Fu, Y X" uniqKey="Fu Y">Y-X Fu</name></author><author><name sortKey="Melero, I" uniqKey="Melero I">I Melero</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rusakiewicz, S" uniqKey="Rusakiewicz S">S Rusakiewicz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Obeid, Jm" uniqKey="Obeid J">JM Obeid</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Berghoff, As" uniqKey="Berghoff A">AS Berghoff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Benci, Jl" uniqKey="Benci J">JL Benci</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sheen Chen, S M" uniqKey="Sheen Chen S">S-M Sheen-Chen</name></author><author><name sortKey="Chen, H S" uniqKey="Chen H">H-S Chen</name></author><author><name sortKey="Eng, H L" uniqKey="Eng H">H-L Eng</name></author><author><name sortKey="Chen, W J" uniqKey="Chen W">W-J Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="El Sarha, Ai" uniqKey="El Sarha A">AI El-Sarha</name></author><author><name sortKey="Magour, Gm" uniqKey="Magour G">GM Magour</name></author><author><name sortKey="Zaki, Sm" uniqKey="Zaki S">SM Zaki</name></author><author><name sortKey="El Sammak, My" uniqKey="El Sammak M">MY El-Sammak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Perik, Pj" uniqKey="Perik P">PJ Perik</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ueno, T" uniqKey="Ueno T">T Ueno</name></author><author><name sortKey="Toi, M" uniqKey="Toi M">M Toi</name></author><author><name sortKey="Tominaga, T" uniqKey="Tominaga T">T Tominaga</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Redondo, P" uniqKey="Redondo P">P Redondo</name></author><author><name 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Tumeh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Taube, Jm" uniqKey="Taube J">JM Taube</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brahmer, Jr" uniqKey="Brahmer J">JR Brahmer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sznol, M" uniqKey="Sznol M">M Sznol</name></author><author><name sortKey="Chen, L" uniqKey="Chen L">L Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lawrence, Ms" uniqKey="Lawrence M">MS Lawrence</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weide, B" uniqKey="Weide B">B Weide</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kruit, Whj" uniqKey="Kruit W">WHJ Kruit</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Escudier, B" uniqKey="Escudier B">B 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Hansen</name><name sortKey="Schmidt, H" sort="Schmidt, H" uniqKey="Schmidt H" first="H." last="Schmidt">H. Schmidt</name><name sortKey="Smyth, M J" sort="Smyth, M J" uniqKey="Smyth M" first="M. J." last="Smyth">M. J. Smyth</name><name sortKey="Svane, I M" sort="Svane, I M" uniqKey="Svane I" first="I. M." last="Svane">I. M. Svane</name></noCountry><country name="France"><noRegion><name sortKey="Jacquelot, N" sort="Jacquelot, N" uniqKey="Jacquelot N" first="N." last="Jacquelot">N. Jacquelot</name></noRegion><name sortKey="Aubin, F" sort="Aubin, F" uniqKey="Aubin F" first="F." last="Aubin">F. Aubin</name><name sortKey="Ayyoub, M" sort="Ayyoub, M" uniqKey="Ayyoub M" first="M." last="Ayyoub">M. Ayyoub</name><name sortKey="Ayyoub, M" sort="Ayyoub, M" uniqKey="Ayyoub M" first="M." last="Ayyoub">M. Ayyoub</name><name sortKey="Balme, B" sort="Balme, B" uniqKey="Balme B" first="B." last="Balme">B. Balme</name><name sortKey="Balme, B" sort="Balme, B" uniqKey="Balme B" first="B." last="Balme">B. 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