AustralieFrV1, Main, Exploration, bibRecord, 003165

Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25

Identifieur interne : 003165 ( Main/Exploration ); précédent : 003164; suivant : 003166

Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25

Auteurs : Dalil Hannani [France] ; Marie Vétizou [France] ; David Enot [France] ; Sylvie Rusakiewicz [France] ; Nathalie Chaput [France] ; David Klatzmann [France] ; Melanie Desbois [France] ; Nicolas Jacquelot [France] ; Nadège Vimond [France] ; Salem Chouaib [France] ; Christine Mateus [France] ; James P. Allison [États-Unis] ; Antoni Ribas [États-Unis] ; Jedd D. Wolchok [États-Unis] ; Jianda Yuan [États-Unis] ; Philip Wong [États-Unis] ; Michael Postow [États-Unis] ; Andrzej Mackiewicz [Pologne] ; Jacek Mackiewicz [Pologne] ; Dirk Schadendorff [Allemagne] ; Dirk Jaeger [Allemagne] ; Alan J. Korman [États-Unis] ; Keith Bahjat [États-Unis] ; Michele Maio [Italie] ; Luana Calabro [Italie] ; Michele Wl Teng [Australie] ; Mark J. Smyth [Australie] ; Alexander Eggermont [France] ; Caroline Robert [France] ; Guido Kroemer [France] ; Laurence Zitvogel [France]

Source :

Cell Research [ 1001-0602 ] ; 2015.

RBID : PMC:4650573

Descripteurs français

KwdFr :
- Adolescent, Adulte, Adulte d'âge moyen, Animaux, Anticorps monoclonaux (pharmacologie), Anticorps monoclonaux (usage thérapeutique), Antigène CTLA-4 (immunologie), Antigène CTLA-4 (métabolisme), Femelle, Humains, Immunothérapie, Jeune adulte, Lymphocytes T CD4+ (immunologie), Lymphocytes T CD4+ (métabolisme), Lymphocytes T régulateurs (immunologie), Modèles animaux de maladie humaine, Mâle, Mélanome (), Mélanome (anatomopathologie), Mélanome (mortalité), Protéines recombinantes (biosynthèse), Protéines recombinantes (génétique), Protéines recombinantes (pharmacologie), Récepteurs à l'interleukine-2 (génétique), Récepteurs à l'interleukine-2 (immunologie), Récepteurs à l'interleukine-2 (métabolisme), Régulation positive (), Souris, Souris de lignée C57BL, Sous-unité alpha du récepteur à l'interleukine-2 (immunologie), Sous-unité alpha du récepteur à l'interleukine-2 (sang), Sujet âgé, Sujet âgé de 80 ans ou plus, Études de cohortes.
MESH :
- anatomopathologie : Mélanome.
- biosynthèse : Protéines recombinantes.
- génétique : Protéines recombinantes, Récepteurs à l'interleukine-2.
- immunologie : Antigène CTLA-4, Lymphocytes T CD4+, Lymphocytes T régulateurs, Récepteurs à l'interleukine-2, Sous-unité alpha du récepteur à l'interleukine-2.
- mortalité : Mélanome.
- métabolisme : Antigène CTLA-4, Lymphocytes T CD4+, Récepteurs à l'interleukine-2.
- pharmacologie : Anticorps monoclonaux, Protéines recombinantes.
- sang : Sous-unité alpha du récepteur à l'interleukine-2.
- usage thérapeutique : Anticorps monoclonaux.
- Adolescent, Adulte, Adulte d'âge moyen, Animaux, Femelle, Humains, Immunothérapie, Jeune adulte, Modèles animaux de maladie humaine, Mâle, Mélanome, Régulation positive, Souris, Souris de lignée C57BL, Sujet âgé, Sujet âgé de 80 ans ou plus, Études de cohortes.

English descriptors

KwdEn :
- Adolescent, Adult, Aged, Aged, 80 and over, Animals, Antibodies, Monoclonal (pharmacology), Antibodies, Monoclonal (therapeutic use), CD4-Positive T-Lymphocytes (immunology), CD4-Positive T-Lymphocytes (metabolism), CTLA-4 Antigen (immunology), CTLA-4 Antigen (metabolism), Cohort Studies, Disease Models, Animal, Female, Humans, Immunotherapy, Interleukin-2 Receptor alpha Subunit (blood), Interleukin-2 Receptor alpha Subunit (immunology), Male, Melanoma (mortality), Melanoma (pathology), Melanoma (therapy), Mice, Mice, Inbred C57BL, Middle Aged, Receptors, Interleukin-2 (genetics), Receptors, Interleukin-2 (immunology), Receptors, Interleukin-2 (metabolism), Recombinant Proteins (biosynthesis), Recombinant Proteins (genetics), Recombinant Proteins (pharmacology), T-Lymphocytes, Regulatory (immunology), Up-Regulation (drug effects), Young Adult.
MESH :
- chemical , biosynthesis : Recombinant Proteins.
- chemical , blood : Interleukin-2 Receptor alpha Subunit.
- chemical , genetics : Receptors, Interleukin-2, Recombinant Proteins.
- chemical , immunology : CTLA-4 Antigen, Interleukin-2 Receptor alpha Subunit, Receptors, Interleukin-2.
- chemical , metabolism : CTLA-4 Antigen, Receptors, Interleukin-2.
- chemical , pharmacology : Antibodies, Monoclonal, Recombinant Proteins.
- chemical , therapeutic use : Antibodies, Monoclonal.
- drug effects : Up-Regulation.
- immunology : CD4-Positive T-Lymphocytes, T-Lymphocytes, Regulatory.
- metabolism : CD4-Positive T-Lymphocytes.
- mortality : Melanoma.
- pathology : Melanoma.
- therapy : Melanoma.
- Adolescent, Adult, Aged, Aged, 80 and over, Animals, Cohort Studies, Disease Models, Animal, Female, Humans, Immunotherapy, Male, Mice, Mice, Inbred C57BL, Middle Aged, Young Adult.

Abstract

The cytotoxic T lymphocyte antigen-4 (CTLA-4)-blocking antibody ipilimumab induces immune-mediated long-term control of metastatic melanoma in a fraction of patients. Although ipilimumab undoubtedly exerts its therapeutic effects via immunostimulation, thus far clinically useful, immunologically relevant biomarkers that predict treatment efficiency have been elusive. Here, we show that neutralization of IL-2 or blocking the α and β subunits of the IL-2 receptor (CD25 and CD122, respectively) abolished the antitumor effects and the accompanying improvement of the ratio of intratumoral T effector versus regulatory cells (Tregs), which were otherwise induced by CTLA-4 blockade in preclinical mouse models. CTLA-4 blockade led to the reduction of a suppressive CD4⁺ T cell subset expressing Lag3, ICOS, IL-10 and Egr2 with a concomitant rise in IL-2-producing effector cells that lost FoxP3 expression and accumulated in regressing tumors. While recombinant IL-2 improved the therapeutic efficacy of CTLA-4 blockade, the decoy IL-2 receptor α (IL-2Rα, sCD25) inhibited the anticancer effects of CTLA-4 blockade. In 262 metastatic melanoma patients receiving ipilimumab, baseline serum concentrations of sCD25 represented an independent indicator of overall survival, with high levels predicting resistance to therapy. Altogether, these results unravel a role for IL-2 and IL-2 receptors in the anticancer activity of CTLA-4 blockade. Importantly, our study provides the first immunologically relevant biomarker, namely elevated serum sCD25, that predicts resistance to CTLA-4 blockade in patients with melanoma.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650573

DOI: 10.1038/cr.2015.3
PubMed: 25582080
PubMed Central: 4650573

Affiliations:

Allemagne, Australie, France, Italie, Pologne, États-Unis

Le document en format XML

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<author><name sortKey="Vimond, Nadege" sort="Vimond, Nadege" uniqKey="Vimond N" first="Nadège" last="Vimond">Nadège Vimond</name>
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<author><name sortKey="Chouaib, Salem" sort="Chouaib, Salem" uniqKey="Chouaib S" first="Salem" last="Chouaib">Salem Chouaib</name>
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<author><name sortKey="Mateus, Christine" sort="Mateus, Christine" uniqKey="Mateus C" first="Christine" last="Mateus">Christine Mateus</name>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="aff10"><institution>Department of Medical Oncology, IGR</institution>
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<author><name sortKey="Allison, James P" sort="Allison, James P" uniqKey="Allison J" first="James P" last="Allison">James P. Allison</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Ribas, Antoni" sort="Ribas, Antoni" uniqKey="Ribas A" first="Antoni" last="Ribas">Antoni Ribas</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Wolchok, Jedd D" sort="Wolchok, Jedd D" uniqKey="Wolchok J" first="Jedd D" last="Wolchok">Jedd D. Wolchok</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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</author>
<author><name sortKey="Yuan, Jianda" sort="Yuan, Jianda" uniqKey="Yuan J" first="Jianda" last="Yuan">Jianda Yuan</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Wong, Philip" sort="Wong, Philip" uniqKey="Wong P" first="Philip" last="Wong">Philip Wong</name>
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, New York, NY,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Postow, Michael" sort="Postow, Michael" uniqKey="Postow M" first="Michael" last="Postow">Michael Postow</name>
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, New York, NY,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mackiewicz, Andrzej" sort="Mackiewicz, Andrzej" uniqKey="Mackiewicz A" first="Andrzej" last="Mackiewicz">Andrzej Mackiewicz</name>
<affiliation wicri:level="1"><nlm:aff id="aff14"><institution>Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre</institution>
, Poznan,<country>Poland</country>
</nlm:aff>
<country xml:lang="fr">Pologne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff15"><institution>Chair of Medical Biotechnology, Poznan University of Medical Sciences</institution>
, Poznan,<country>Poland</country>
</nlm:aff>
<country xml:lang="fr">Pologne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mackiewicz, Jacek" sort="Mackiewicz, Jacek" uniqKey="Mackiewicz J" first="Jacek" last="Mackiewicz">Jacek Mackiewicz</name>
<affiliation wicri:level="1"><nlm:aff id="aff14"><institution>Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre</institution>
, Poznan,<country>Poland</country>
</nlm:aff>
<country xml:lang="fr">Pologne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff15"><institution>Chair of Medical Biotechnology, Poznan University of Medical Sciences</institution>
, Poznan,<country>Poland</country>
</nlm:aff>
<country xml:lang="fr">Pologne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Schadendorff, Dirk" sort="Schadendorff, Dirk" uniqKey="Schadendorff D" first="Dirk" last="Schadendorff">Dirk Schadendorff</name>
<affiliation wicri:level="1"><nlm:aff id="aff16"><institution>Department of Dermatology, University Hospital Essen</institution>
,<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Jaeger, Dirk" sort="Jaeger, Dirk" uniqKey="Jaeger D" first="Dirk" last="Jaeger">Dirk Jaeger</name>
<affiliation wicri:level="1"><nlm:aff id="aff17"><institution>National Center for Tumor Diseases, University Hospital</institution>
, Heidelberg,<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Korman, Alan J" sort="Korman, Alan J" uniqKey="Korman A" first="Alan J" last="Korman">Alan J. Korman</name>
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, Redwood City, CA,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bahjat, Keith" sort="Bahjat, Keith" uniqKey="Bahjat K" first="Keith" last="Bahjat">Keith Bahjat</name>
<affiliation wicri:level="1"><nlm:aff id="aff19"><institution>Earle A Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center</institution>
, Portland, OR,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Maio, Michele" sort="Maio, Michele" uniqKey="Maio M" first="Michele" last="Maio">Michele Maio</name>
<affiliation wicri:level="1"><nlm:aff id="aff20"><institution>Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Istituto Toscano Tumori</institution>
, Siena,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Calabro, Luana" sort="Calabro, Luana" uniqKey="Calabro L" first="Luana" last="Calabro">Luana Calabro</name>
<affiliation wicri:level="1"><nlm:aff id="aff20"><institution>Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Istituto Toscano Tumori</institution>
, Siena,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Teng, Michele Wl" sort="Teng, Michele Wl" uniqKey="Teng M" first="Michele Wl" last="Teng">Michele Wl Teng</name>
<affiliation wicri:level="1"><nlm:aff id="aff21"><institution>QIMR Berghofer Medical Research Institute</institution>
, Herston, 4006, Queensland,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff22"><institution>School of Medicine, The University of Queensland</institution>
, Herston, QLD 4006, Queensland,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Smyth, Mark J" sort="Smyth, Mark J" uniqKey="Smyth M" first="Mark J" last="Smyth">Mark J. Smyth</name>
<affiliation wicri:level="1"><nlm:aff id="aff21"><institution>QIMR Berghofer Medical Research Institute</institution>
, Herston, 4006, Queensland,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff22"><institution>School of Medicine, The University of Queensland</institution>
, Herston, QLD 4006, Queensland,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Eggermont, Alexander" sort="Eggermont, Alexander" uniqKey="Eggermont A" first="Alexander" last="Eggermont">Alexander Eggermont</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Gustave Roussy Cancer Campus</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>INSERM U1015</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff23"><institution>INSERM U981</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Robert, Caroline" sort="Robert, Caroline" uniqKey="Robert C" first="Caroline" last="Robert">Caroline Robert</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Gustave Roussy Cancer Campus</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>INSERM U1015</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff10"><institution>Department of Medical Oncology, IGR</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff23"><institution>INSERM U981</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kroemer, Guido" sort="Kroemer, Guido" uniqKey="Kroemer G" first="Guido" last="Kroemer">Guido Kroemer</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Gustave Roussy Cancer Campus</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff4"><institution>INSERM U848</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Metabolomics Platform, Institut Gustave Roussy</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff24"><institution>Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138</institution>
, Paris,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff25"><institution>Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP</institution>
, Paris,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff26"><institution>Université Paris Descartes, Sorbonne Paris Cité</institution>
, Paris,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zitvogel, Laurence" sort="Zitvogel, Laurence" uniqKey="Zitvogel L" first="Laurence" last="Zitvogel">Laurence Zitvogel</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Gustave Roussy Cancer Campus</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>INSERM U1015</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Université Paris Sud-XI, Faculté de Médecine</institution>
, Le Kremlin Bicêtre,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff10"><institution>Department of Medical Oncology, IGR</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">25582080</idno>
<idno type="pmc">4650573</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650573</idno>
<idno type="RBID">PMC:4650573</idno>
<idno type="doi">10.1038/cr.2015.3</idno>
<date when="2015">2015</date>
<idno type="wicri:Area/Pmc/Corpus">000695</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000695</idno>
<idno type="wicri:Area/Pmc/Curation">000694</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000694</idno>
<idno type="wicri:Area/Pmc/Checkpoint">001177</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001177</idno>
<idno type="wicri:source">PubMed</idno>
<idno type="wicri:Area/PubMed/Corpus">003013</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">003013</idno>
<idno type="wicri:Area/PubMed/Curation">002F32</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002F32</idno>
<idno type="wicri:Area/PubMed/Checkpoint">002F32</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002F32</idno>
<idno type="wicri:Area/Ncbi/Merge">002159</idno>
<idno type="wicri:Area/Ncbi/Curation">002159</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">002159</idno>
<idno type="wicri:doubleKey">1001-0602:2015:Hannani D:anticancer:immunotherapy:by</idno>
<idno type="wicri:Area/Main/Merge">003166</idno>
<idno type="wicri:Area/Main/Curation">003165</idno>
<idno type="wicri:Area/Main/Exploration">003165</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25</title>
<author><name sortKey="Hannani, Dalil" sort="Hannani, Dalil" uniqKey="Hannani D" first="Dalil" last="Hannani">Dalil Hannani</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Gustave Roussy Cancer Campus</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>INSERM U1015</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Université Paris Sud-XI, Faculté de Médecine</institution>
, Le Kremlin Bicêtre,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Vetizou, Marie" sort="Vetizou, Marie" uniqKey="Vetizou M" first="Marie" last="Vétizou">Marie Vétizou</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Gustave Roussy Cancer Campus</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>INSERM U1015</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Université Paris Sud-XI, Faculté de Médecine</institution>
, Le Kremlin Bicêtre,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Enot, David" sort="Enot, David" uniqKey="Enot D" first="David" last="Enot">David Enot</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Gustave Roussy Cancer Campus</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff4"><institution>INSERM U848</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Metabolomics Platform, Institut Gustave Roussy</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Rusakiewicz, Sylvie" sort="Rusakiewicz, Sylvie" uniqKey="Rusakiewicz S" first="Sylvie" last="Rusakiewicz">Sylvie Rusakiewicz</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Gustave Roussy Cancer Campus</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>INSERM U1015</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 507</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Chaput, Nathalie" sort="Chaput, Nathalie" uniqKey="Chaput N" first="Nathalie" last="Chaput">Nathalie Chaput</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Gustave Roussy Cancer Campus</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>INSERM U1015</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 507</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Klatzmann, David" sort="Klatzmann, David" uniqKey="Klatzmann D" first="David" last="Klatzmann">David Klatzmann</name>
<affiliation wicri:level="1"><nlm:aff id="aff7"><institution>INSERM, Unité Mixte de Recherche_S959, I<sup>3</sup>
</institution>
, Paris,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff8"><institution>Assistance-Publique Hopitaux de Paris, Hôpital Pitié-Salpêtrière, Biotherapy</institution>
, Paris,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Desbois, Melanie" sort="Desbois, Melanie" uniqKey="Desbois M" first="Melanie" last="Desbois">Melanie Desbois</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Gustave Roussy Cancer Campus</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>INSERM U1015</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 507</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Jacquelot, Nicolas" sort="Jacquelot, Nicolas" uniqKey="Jacquelot N" first="Nicolas" last="Jacquelot">Nicolas Jacquelot</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Gustave Roussy Cancer Campus</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>INSERM U1015</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Université Paris Sud-XI, Faculté de Médecine</institution>
, Le Kremlin Bicêtre,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Vimond, Nadege" sort="Vimond, Nadege" uniqKey="Vimond N" first="Nadège" last="Vimond">Nadège Vimond</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Gustave Roussy Cancer Campus</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>INSERM U1015</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 507</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Chouaib, Salem" sort="Chouaib, Salem" uniqKey="Chouaib S" first="Salem" last="Chouaib">Salem Chouaib</name>
<affiliation wicri:level="1"><nlm:aff id="aff9"><institution>INSERM U753</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mateus, Christine" sort="Mateus, Christine" uniqKey="Mateus C" first="Christine" last="Mateus">Christine Mateus</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Gustave Roussy Cancer Campus</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff10"><institution>Department of Medical Oncology, IGR</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Allison, James P" sort="Allison, James P" uniqKey="Allison J" first="James P" last="Allison">James P. Allison</name>
<affiliation wicri:level="1"><nlm:aff id="aff11"><institution>Department of Immunology, MD Anderson Cancer Center</institution>
, Houston, TX,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ribas, Antoni" sort="Ribas, Antoni" uniqKey="Ribas A" first="Antoni" last="Ribas">Antoni Ribas</name>
<affiliation wicri:level="1"><nlm:aff id="aff12"><institution>University of California Los Angeles</institution>
, Los Angeles, CA,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wolchok, Jedd D" sort="Wolchok, Jedd D" uniqKey="Wolchok J" first="Jedd D" last="Wolchok">Jedd D. Wolchok</name>
<affiliation wicri:level="1"><nlm:aff id="aff13"><institution>Ludwig Center for Cancer Immunotherapy, Department of Immunology, and Department of Medicine, Memorial Sloan-Kettering Cancer Center</institution>
, New York, NY,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Yuan, Jianda" sort="Yuan, Jianda" uniqKey="Yuan J" first="Jianda" last="Yuan">Jianda Yuan</name>
<affiliation wicri:level="1"><nlm:aff id="aff13"><institution>Ludwig Center for Cancer Immunotherapy, Department of Immunology, and Department of Medicine, Memorial Sloan-Kettering Cancer Center</institution>
, New York, NY,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wong, Philip" sort="Wong, Philip" uniqKey="Wong P" first="Philip" last="Wong">Philip Wong</name>
<affiliation wicri:level="1"><nlm:aff id="aff13"><institution>Ludwig Center for Cancer Immunotherapy, Department of Immunology, and Department of Medicine, Memorial Sloan-Kettering Cancer Center</institution>
, New York, NY,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Postow, Michael" sort="Postow, Michael" uniqKey="Postow M" first="Michael" last="Postow">Michael Postow</name>
<affiliation wicri:level="1"><nlm:aff id="aff13"><institution>Ludwig Center for Cancer Immunotherapy, Department of Immunology, and Department of Medicine, Memorial Sloan-Kettering Cancer Center</institution>
, New York, NY,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mackiewicz, Andrzej" sort="Mackiewicz, Andrzej" uniqKey="Mackiewicz A" first="Andrzej" last="Mackiewicz">Andrzej Mackiewicz</name>
<affiliation wicri:level="1"><nlm:aff id="aff14"><institution>Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre</institution>
, Poznan,<country>Poland</country>
</nlm:aff>
<country xml:lang="fr">Pologne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff15"><institution>Chair of Medical Biotechnology, Poznan University of Medical Sciences</institution>
, Poznan,<country>Poland</country>
</nlm:aff>
<country xml:lang="fr">Pologne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mackiewicz, Jacek" sort="Mackiewicz, Jacek" uniqKey="Mackiewicz J" first="Jacek" last="Mackiewicz">Jacek Mackiewicz</name>
<affiliation wicri:level="1"><nlm:aff id="aff14"><institution>Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre</institution>
, Poznan,<country>Poland</country>
</nlm:aff>
<country xml:lang="fr">Pologne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff15"><institution>Chair of Medical Biotechnology, Poznan University of Medical Sciences</institution>
, Poznan,<country>Poland</country>
</nlm:aff>
<country xml:lang="fr">Pologne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Schadendorff, Dirk" sort="Schadendorff, Dirk" uniqKey="Schadendorff D" first="Dirk" last="Schadendorff">Dirk Schadendorff</name>
<affiliation wicri:level="1"><nlm:aff id="aff16"><institution>Department of Dermatology, University Hospital Essen</institution>
,<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Jaeger, Dirk" sort="Jaeger, Dirk" uniqKey="Jaeger D" first="Dirk" last="Jaeger">Dirk Jaeger</name>
<affiliation wicri:level="1"><nlm:aff id="aff17"><institution>National Center for Tumor Diseases, University Hospital</institution>
, Heidelberg,<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Korman, Alan J" sort="Korman, Alan J" uniqKey="Korman A" first="Alan J" last="Korman">Alan J. Korman</name>
<affiliation wicri:level="1"><nlm:aff id="aff18"><institution>Bristol-Myers Squibb</institution>
, Redwood City, CA,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bahjat, Keith" sort="Bahjat, Keith" uniqKey="Bahjat K" first="Keith" last="Bahjat">Keith Bahjat</name>
<affiliation wicri:level="1"><nlm:aff id="aff19"><institution>Earle A Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center</institution>
, Portland, OR,<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Maio, Michele" sort="Maio, Michele" uniqKey="Maio M" first="Michele" last="Maio">Michele Maio</name>
<affiliation wicri:level="1"><nlm:aff id="aff20"><institution>Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Istituto Toscano Tumori</institution>
, Siena,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Calabro, Luana" sort="Calabro, Luana" uniqKey="Calabro L" first="Luana" last="Calabro">Luana Calabro</name>
<affiliation wicri:level="1"><nlm:aff id="aff20"><institution>Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Istituto Toscano Tumori</institution>
, Siena,<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Teng, Michele Wl" sort="Teng, Michele Wl" uniqKey="Teng M" first="Michele Wl" last="Teng">Michele Wl Teng</name>
<affiliation wicri:level="1"><nlm:aff id="aff21"><institution>QIMR Berghofer Medical Research Institute</institution>
, Herston, 4006, Queensland,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff22"><institution>School of Medicine, The University of Queensland</institution>
, Herston, QLD 4006, Queensland,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Smyth, Mark J" sort="Smyth, Mark J" uniqKey="Smyth M" first="Mark J" last="Smyth">Mark J. Smyth</name>
<affiliation wicri:level="1"><nlm:aff id="aff21"><institution>QIMR Berghofer Medical Research Institute</institution>
, Herston, 4006, Queensland,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff22"><institution>School of Medicine, The University of Queensland</institution>
, Herston, QLD 4006, Queensland,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Eggermont, Alexander" sort="Eggermont, Alexander" uniqKey="Eggermont A" first="Alexander" last="Eggermont">Alexander Eggermont</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Gustave Roussy Cancer Campus</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>INSERM U1015</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff23"><institution>INSERM U981</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Robert, Caroline" sort="Robert, Caroline" uniqKey="Robert C" first="Caroline" last="Robert">Caroline Robert</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Gustave Roussy Cancer Campus</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>INSERM U1015</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff10"><institution>Department of Medical Oncology, IGR</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff23"><institution>INSERM U981</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kroemer, Guido" sort="Kroemer, Guido" uniqKey="Kroemer G" first="Guido" last="Kroemer">Guido Kroemer</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Gustave Roussy Cancer Campus</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff4"><institution>INSERM U848</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Metabolomics Platform, Institut Gustave Roussy</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff24"><institution>Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138</institution>
, Paris,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff25"><institution>Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP</institution>
, Paris,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff26"><institution>Université Paris Descartes, Sorbonne Paris Cité</institution>
, Paris,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zitvogel, Laurence" sort="Zitvogel, Laurence" uniqKey="Zitvogel L" first="Laurence" last="Zitvogel">Laurence Zitvogel</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Gustave Roussy Cancer Campus</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>INSERM U1015</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Université Paris Sud-XI, Faculté de Médecine</institution>
, Le Kremlin Bicêtre,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff10"><institution>Department of Medical Oncology, IGR</institution>
, Villejuif,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Cell Research</title>
<idno type="ISSN">1001-0602</idno>
<idno type="eISSN">1748-7838</idno>
<imprint><date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term>
<term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Animals</term>
<term>Antibodies, Monoclonal (pharmacology)</term>
<term>Antibodies, Monoclonal (therapeutic use)</term>
<term>CD4-Positive T-Lymphocytes (immunology)</term>
<term>CD4-Positive T-Lymphocytes (metabolism)</term>
<term>CTLA-4 Antigen (immunology)</term>
<term>CTLA-4 Antigen (metabolism)</term>
<term>Cohort Studies</term>
<term>Disease Models, Animal</term>
<term>Female</term>
<term>Humans</term>
<term>Immunotherapy</term>
<term>Interleukin-2 Receptor alpha Subunit (blood)</term>
<term>Interleukin-2 Receptor alpha Subunit (immunology)</term>
<term>Male</term>
<term>Melanoma (mortality)</term>
<term>Melanoma (pathology)</term>
<term>Melanoma (therapy)</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Middle Aged</term>
<term>Receptors, Interleukin-2 (genetics)</term>
<term>Receptors, Interleukin-2 (immunology)</term>
<term>Receptors, Interleukin-2 (metabolism)</term>
<term>Recombinant Proteins (biosynthesis)</term>
<term>Recombinant Proteins (genetics)</term>
<term>Recombinant Proteins (pharmacology)</term>
<term>T-Lymphocytes, Regulatory (immunology)</term>
<term>Up-Regulation (drug effects)</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adolescent</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Animaux</term>
<term>Anticorps monoclonaux (pharmacologie)</term>
<term>Anticorps monoclonaux (usage thérapeutique)</term>
<term>Antigène CTLA-4 (immunologie)</term>
<term>Antigène CTLA-4 (métabolisme)</term>
<term>Femelle</term>
<term>Humains</term>
<term>Immunothérapie</term>
<term>Jeune adulte</term>
<term>Lymphocytes T CD4+ (immunologie)</term>
<term>Lymphocytes T CD4+ (métabolisme)</term>
<term>Lymphocytes T régulateurs (immunologie)</term>
<term>Modèles animaux de maladie humaine</term>
<term>Mâle</term>
<term>Mélanome ()</term>
<term>Mélanome (anatomopathologie)</term>
<term>Mélanome (mortalité)</term>
<term>Protéines recombinantes (biosynthèse)</term>
<term>Protéines recombinantes (génétique)</term>
<term>Protéines recombinantes (pharmacologie)</term>
<term>Récepteurs à l'interleukine-2 (génétique)</term>
<term>Récepteurs à l'interleukine-2 (immunologie)</term>
<term>Récepteurs à l'interleukine-2 (métabolisme)</term>
<term>Régulation positive ()</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Sous-unité alpha du récepteur à l'interleukine-2 (immunologie)</term>
<term>Sous-unité alpha du récepteur à l'interleukine-2 (sang)</term>
<term>Sujet âgé</term>
<term>Sujet âgé de 80 ans ou plus</term>
<term>Études de cohortes</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Recombinant Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Interleukin-2 Receptor alpha Subunit</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Receptors, Interleukin-2</term>
<term>Recombinant Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>CTLA-4 Antigen</term>
<term>Interleukin-2 Receptor alpha Subunit</term>
<term>Receptors, Interleukin-2</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>CTLA-4 Antigen</term>
<term>Receptors, Interleukin-2</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antibodies, Monoclonal</term>
<term>Recombinant Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antibodies, Monoclonal</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Mélanome</term>
</keywords>
<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Protéines recombinantes</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Up-Regulation</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Protéines recombinantes</term>
<term>Récepteurs à l'interleukine-2</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Antigène CTLA-4</term>
<term>Lymphocytes T CD4+</term>
<term>Lymphocytes T régulateurs</term>
<term>Récepteurs à l'interleukine-2</term>
<term>Sous-unité alpha du récepteur à l'interleukine-2</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term>
<term>T-Lymphocytes, Regulatory</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Melanoma</term>
</keywords>
<keywords scheme="MESH" qualifier="mortalité" xml:lang="fr"><term>Mélanome</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antigène CTLA-4</term>
<term>Lymphocytes T CD4+</term>
<term>Récepteurs à l'interleukine-2</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Melanoma</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Anticorps monoclonaux</term>
<term>Protéines recombinantes</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Sous-unité alpha du récepteur à l'interleukine-2</term>
</keywords>
<keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Melanoma</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Anticorps monoclonaux</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adolescent</term>
<term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Animals</term>
<term>Cohort Studies</term>
<term>Disease Models, Animal</term>
<term>Female</term>
<term>Humans</term>
<term>Immunotherapy</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Middle Aged</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adolescent</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Animaux</term>
<term>Femelle</term>
<term>Humains</term>
<term>Immunothérapie</term>
<term>Jeune adulte</term>
<term>Modèles animaux de maladie humaine</term>
<term>Mâle</term>
<term>Mélanome</term>
<term>Régulation positive</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Sujet âgé</term>
<term>Sujet âgé de 80 ans ou plus</term>
<term>Études de cohortes</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>The cytotoxic T lymphocyte antigen-4 (CTLA-4)-blocking antibody ipilimumab induces immune-mediated long-term control of metastatic melanoma in a fraction of patients. Although ipilimumab undoubtedly exerts its therapeutic effects via immunostimulation, thus far clinically useful, immunologically relevant biomarkers that predict treatment efficiency have been elusive. Here, we show that neutralization of IL-2 or blocking the α and β subunits of the IL-2 receptor (CD25 and CD122, respectively) abolished the antitumor effects and the accompanying improvement of the ratio of intratumoral T effector versus regulatory cells (Tregs), which were otherwise induced by CTLA-4 blockade in preclinical mouse models. CTLA-4 blockade led to the reduction of a suppressive CD4<sup>+</sup>
 T cell subset expressing Lag3, ICOS, IL-10 and Egr2 with a concomitant rise in IL-2-producing effector cells that lost FoxP3 expression and accumulated in regressing tumors. While recombinant IL-2 improved the therapeutic efficacy of CTLA-4 blockade, the decoy IL-2 receptor α (IL-2Rα, sCD25) inhibited the anticancer effects of CTLA-4 blockade. In 262 metastatic melanoma patients receiving ipilimumab, baseline serum concentrations of sCD25 represented an independent indicator of overall survival, with high levels predicting resistance to therapy. Altogether, these results unravel a role for IL-2 and IL-2 receptors in the anticancer activity of CTLA-4 blockade. Importantly, our study provides the first immunologically relevant biomarker, namely elevated serum sCD25, that predicts resistance to CTLA-4 blockade in patients with melanoma.</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>Allemagne</li>
<li>Australie</li>
<li>France</li>
<li>Italie</li>
<li>Pologne</li>
<li>États-Unis</li>
</country>
</list>
<tree><country name="France"><noRegion><name sortKey="Hannani, Dalil" sort="Hannani, Dalil" uniqKey="Hannani D" first="Dalil" last="Hannani">Dalil Hannani</name>
</noRegion>
<name sortKey="Chaput, Nathalie" sort="Chaput, Nathalie" uniqKey="Chaput N" first="Nathalie" last="Chaput">Nathalie Chaput</name>
<name sortKey="Chaput, Nathalie" sort="Chaput, Nathalie" uniqKey="Chaput N" first="Nathalie" last="Chaput">Nathalie Chaput</name>
<name sortKey="Chaput, Nathalie" sort="Chaput, Nathalie" uniqKey="Chaput N" first="Nathalie" last="Chaput">Nathalie Chaput</name>
<name sortKey="Chouaib, Salem" sort="Chouaib, Salem" uniqKey="Chouaib S" first="Salem" last="Chouaib">Salem Chouaib</name>
<name sortKey="Desbois, Melanie" sort="Desbois, Melanie" uniqKey="Desbois M" first="Melanie" last="Desbois">Melanie Desbois</name>
<name sortKey="Desbois, Melanie" sort="Desbois, Melanie" uniqKey="Desbois M" first="Melanie" last="Desbois">Melanie Desbois</name>
<name sortKey="Desbois, Melanie" sort="Desbois, Melanie" uniqKey="Desbois M" first="Melanie" last="Desbois">Melanie Desbois</name>
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<country name="Pologne"><noRegion><name sortKey="Mackiewicz, Andrzej" sort="Mackiewicz, Andrzej" uniqKey="Mackiewicz A" first="Andrzej" last="Mackiewicz">Andrzej Mackiewicz</name>
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   |texte=   Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25
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Serveur d'exploration sur les relations entre la France et l'Australie

Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25

Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25

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	Serveur d'exploration sur les relations entre la France et l'Australie
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