G. Long, D. Stroyakovskiy, H. Gogas, E. Levchenko, F. De-braud et al., Combined BRAF and MEK Inhibition versus BRAF Inhibition Alone in Melanoma, New England Journal of Medicine, vol.371, issue.20, pp.1877-88, 2014.
DOI : 10.1056/NEJMoa1406037

URL : https://air.unimi.it/bitstream/2434/425634/2/NewEnglandJournMedicine_CombinedGraf_2014.pdf

P. Chapman, A. Hauschild, C. Robert, J. Haanen, P. Ascierto et al., Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation, New England Journal of Medicine, vol.364, issue.26, pp.2507-2523, 2011.
DOI : 10.1056/NEJMoa1103782

F. Hodi, O. Day, S. Mcdermott, D. Weber, R. Sosman et al., Improved Survival with Ipilimumab in Patients with Metastatic Melanoma, New England Journal of Medicine, vol.363, issue.8, pp.711-734, 2010.
DOI : 10.1056/NEJMoa1003466

URL : http://www.nejm.org/doi/pdf/10.1056/NEJMoa1003466

C. Robert, J. Schachter, G. Long, A. Arance, J. Grob et al., Pembrolizumab versus Ipilimumab in Advanced Melanoma, New England Journal of Medicine, vol.372, issue.26, pp.2521-2553, 2015.
DOI : 10.1056/NEJMoa1503093

J. Larkin, V. Chiarion-sileni, R. Gonzalez, J. Grob, C. Cowey et al., Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma, New England Journal of Medicine, vol.373, issue.1, pp.23-34, 2015.
DOI : 10.1056/NEJMoa1504030

URL : http://www.zora.uzh.ch/id/eprint/113016/1/608_Larkin%20et%20al%20_NEJM%202015.pdf

D. Schadendorf, F. Hodi, C. Robert, J. Weber, K. Margolin et al., Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma, Journal of Clinical Oncology, vol.33, issue.17, pp.1889-94, 2015.
DOI : 10.1200/JCO.2014.56.2736

C. Robert, L. Thomas, I. Bondarenko, O. Day, S. Weber et al., Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma, New England Journal of Medicine, vol.364, issue.26, pp.2517-2543, 2011.
DOI : 10.1056/NEJMoa1104621

J. Egen, M. Kuhns, and J. Allison, CTLA-4: new insights into its biological function and use in tumor immunotherapy, Nature Immunology, vol.98, issue.7, pp.611-619, 2002.
DOI : 10.1073/pnas.251140998

M. Miyara, Y. Yoshioka, A. Kitoh, T. Shima, K. Wing et al., Functional Delineation and Differentiation Dynamics of Human CD4+ T Cells Expressing the FoxP3 Transcription Factor, Immunity, vol.30, issue.6, pp.899-911, 2009.
DOI : 10.1016/j.immuni.2009.03.019

URL : https://doi.org/10.1016/j.immuni.2009.03.019

A. Collins, D. Brodie, R. Gilbert, A. Iaboni, R. Manso-sancho et al., The Interaction Properties of Costimulatory Molecules Revisited, Immunity, vol.17, issue.2, pp.201-211, 2002.
DOI : 10.1016/S1074-7613(02)00362-X

URL : https://doi.org/10.1016/s1074-7613(02)00362-x

J. Wolchok and Y. Saenger, The Mechanism of Anti-CTLA-4 Activity and the Negative Regulation of T-Cell Activation, The Oncologist, vol.13, issue.Supplement 4, pp.2-9, 2008.
DOI : 10.1634/theoncologist.13-S4-2

P. Linsley, W. Brady, M. Urnes, L. Grosmaire, N. Damle et al., CTLA-4 is a second receptor for the B cell activation antigen B7, Journal of Experimental Medicine, vol.174, issue.3, pp.561-570, 1991.
DOI : 10.1084/jem.174.3.561

URL : http://jem.rupress.org/content/jem/174/3/561.full.pdf

C. Chambers, M. Kuhns, J. Egen, and J. Allison, : Mechanisms and Manipulation in Tumor Immunotherapy, Annual Review of Immunology, vol.19, issue.1, pp.565-94, 2001.
DOI : 10.1146/annurev.immunol.19.1.565

R. Greenwald, V. Boussiotis, R. Lorsbach, A. Abbas, and A. Sharpe, CTLA-4 Regulates Induction of Anergy In Vivo, Immunity, vol.14, issue.2, pp.145-55, 2001.
DOI : 10.1016/S1074-7613(01)00097-8

N. Hunder, H. Wallen, J. Cao, D. Hendricks, J. Reilly et al., Treatment of Metastatic Melanoma with Autologous CD4+ T Cells against NY-ESO-1, New England Journal of Medicine, vol.358, issue.25, pp.2698-703, 2008.
DOI : 10.1056/NEJMoa0800251

URL : http://europepmc.org/articles/pmc3277288?pdf=render

J. Yuan, M. Adamow, B. Ginsberg, T. Rasalan, E. Ritter et al., Integrated NY-ESO-1 antibody and CD8+ T-cell responses correlate with clinical benefit in advanced melanoma patients treated with ipilimumab, Proceedings of the National Academy of Sciences, vol.11, issue.7, pp.16723-16731, 2011.
DOI : 10.3109/14653240903136987

URL : http://www.pnas.org/content/108/40/16723.full.pdf

B. Weide, H. Zelba, E. Derhovanessian, A. Pflugfelder, T. Eigentler et al., Functional T Cells Targeting NY-ESO-1 or Melan-A Are Predictive for Survival of Patients With Distant Melanoma Metastasis, Journal of Clinical Oncology, vol.30, issue.15, pp.1835-1876, 2012.
DOI : 10.1200/JCO.2011.40.2271

URL : http://espace.library.uq.edu.au/view/UQ:412319/UQ412319_OA.pdf

A. Snyder, V. Makarov, T. Merghoub, J. Yuan, J. Zaretsky et al., Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma, New England Journal of Medicine, vol.371, issue.23, pp.2189-99, 2014.
DOI : 10.1056/NEJMoa1406498

N. Van-rooij, M. Van-buuren, D. Philips, A. Velds, M. Toebes et al., Tumor Exome Analysis Reveals Neoantigen-Specific T-Cell Reactivity in an Ipilimumab-Responsive Melanoma, Journal of Clinical Oncology, vol.31, issue.32, pp.439-481, 2013.
DOI : 10.1200/JCO.2012.47.7521

P. Jr, D. Dudley, M. Robbins, P. Rosenberg, and S. , Transition of late-stage effector T cells to CD27þ CD28þ tumorreactive effector memory T cells in humans after adoptive cell transfer therapy, Blood, vol.105, issue.1, pp.241-50, 2005.

K. Wistuba-hamprecht, D. Benedetto, S. Schilling, B. Sucker, A. Schadendorf et al., Phenotypic characterization and prognostic impact of circulating ???? and ???? T-cells in metastatic malignant melanoma, International Journal of Cancer, vol.138, issue.3, pp.698-704, 2016.
DOI : 10.1016/j.bbrc.2007.01.031

URL : http://onlinelibrary.wiley.com/doi/10.1002/ijc.29818/pdf

J. Delyon, C. Mateus, D. Lefeuvre, E. Lanoy, L. Zitvogel et al., Experience in daily practice with ipilimumab for the treatment of patients with metastatic melanoma: an early increase in lymphocyte and eosinophil counts is associated with improved survival, Annals of Oncology, vol.62, issue.6, pp.1697-703, 2013.
DOI : 10.1111/j.1365-3083.2005.01682.x

G. Ku, J. Yuan, D. Page, S. Schroeder, K. Panageas et al., Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting, Cancer, vol.27, issue.22 pt 1, pp.1767-75, 2010.
DOI : 10.4049/jimmunol.175.11.7746

URL : http://onlinelibrary.wiley.com/doi/10.1002/cncr.24951/pdf

A. Sarnaik, Y. B. Yu, D. Morelli, D. Hall, M. Bogle et al., Extended Dose Ipilimumab with a Peptide Vaccine: Immune Correlates Associated with Clinical Benefit in Patients with Resected High-Risk Stage IIIc/IV Melanoma, Clinical Cancer Research, vol.17, issue.4, pp.896-906, 2011.
DOI : 10.1158/1078-0432.CCR-10-2463

URL : http://clincancerres.aacrjournals.org/content/clincanres/17/4/896.full.pdf

A. Tarhini, H. Edington, L. Butterfield, Y. Lin, Y. Shuai et al., Immune Monitoring of the Circulation and the Tumor Microenvironment in Patients with Regionally Advanced Melanoma Receiving Neoadjuvant Ipilimumab, PLoS ONE, vol.72, issue.2, p.87705, 2014.
DOI : 10.1371/journal.pone.0087705.s007

E. Simeone, G. Gentilcore, D. Giannarelli, A. Grimaldi, C. Caraco et al., Immunological and biological changes during ipilimumab treatment and their potential correlation with clinical response and survival in patients with advanced melanoma, Cancer Immunology, Immunotherapy, vol.60, issue.7, pp.675-83, 2014.
DOI : 10.1007/s00262-011-1046-y

E. Romano, M. Kusio-kobialka, P. Foukas, P. Baumgaertner, C. Meyer et al., Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patients, Proceedings of the National Academy of Sciences, vol.4, issue.3, pp.6140-6145, 2015.
DOI : 10.1073/pnas.0712237105

URL : http://www.pnas.org/content/112/19/6140.full.pdf

R. Huang, J. Jalil, J. Economou, B. Chmielowski, R. Koya et al., CTLA4 Blockade Induces Frequent Tumor Infiltration by Activated Lymphocytes Regardless of Clinical Responses in Humans, Clinical Cancer Research, vol.17, issue.12, pp.4101-4110, 2011.
DOI : 10.1158/1078-0432.CCR-11-0407

URL : http://clincancerres.aacrjournals.org/content/clincanres/17/12/4101.full.pdf

A. Maker, P. Attia, and S. Rosenberg, Analysis of the Cellular Mechanism of Antitumor Responses and Autoimmunity in Patients Treated with CTLA-4 Blockade, The Journal of Immunology, vol.175, issue.11, pp.7746-54, 2005.
DOI : 10.4049/jimmunol.175.11.7746

P. Sharma, K. Wagner, J. Wolchok, and J. Allison, Novel cancer immunotherapy agents with survival benefit: recent successes and next steps, Nature Reviews Cancer, vol.208, issue.11, pp.805-817, 2011.
DOI : 10.1084/jem.20100619

URL : http://europepmc.org/articles/pmc3426440?pdf=render

A. Martens, K. Wistuba-hamprecht, J. Yuan, M. Postow, P. Wong et al., Increases in Absolute Lymphocytes and Circulating CD4+ and CD8+ T Cells Are Associated with Positive Clinical Outcome of Melanoma Patients Treated with Ipilimumab, Clinical Cancer Research, vol.22, issue.19, pp.4848-58, 2016.
DOI : 10.1158/1078-0432.CCR-16-0249

URL : https://hal.archives-ouvertes.fr/inserm-01408937

V. Pedicord, W. Montalvo, I. Leiner, and J. Allison, Single dose of anti-CTLA-4 enhances CD8+ T-cell memory formation, function, and maintenance, Proceedings of the National Academy of Sciences, vol.94, issue.17, pp.266-71, 2011.
DOI : 10.1073/pnas.94.17.9296

URL : http://www.pnas.org/content/108/1/266.full.pdf

M. Krummel and J. Allison, CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells, Journal of Experimental Medicine, vol.183, issue.6, pp.2533-2573, 1996.
DOI : 10.1084/jem.183.6.2533

URL : http://jem.rupress.org/content/jem/183/6/2533.full.pdf

K. Peggs, S. Quezada, C. Chambers, A. Korman, and J. Allison, Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti???CTLA-4 antibodies, The Journal of Experimental Medicine, vol.59, issue.8, pp.1717-1742, 2009.
DOI : 10.1126/science.1160062

J. Felix, J. Lambert, M. Roelens, E. Maubec, H. Guermouche et al., Ipilimumab reshapes T cell memory subsets in melanoma patients with clinical response, OncoImmunology, vol.5, issue.7, p.1136045, 2016.
DOI : 10.1371/journal.pone.0067401

URL : http://www.tandfonline.com/doi/pdf/10.1080/2162402X.2015.1136045?needAccess=true

L. Baitsch, A. Legat, L. Barba, F. Marraco, S. Rivals et al., Extended Co-Expression of Inhibitory Receptors by Human CD8 T-Cells Depending on Differentiation, Antigen-Specificity and Anatomical Localization, PLoS ONE, vol.185, issue.2, p.30852, 2012.
DOI : 10.1371/journal.pone.0030852.s006

URL : http://doi.org/10.1371/journal.pone.0030852

A. Gros, P. Robbins, X. Yao, Y. Li, S. Turcotte et al., PD-1 identifies the patient-specific CD8+ tumor-reactive repertoire infiltrating human tumors, Journal of Clinical Investigation, vol.124, issue.5, pp.2246-59, 2014.
DOI : 10.1172/JCI73639DS1

URL : http://www.jci.org/articles/view/73639/files/pdf

A. Gros, M. Parkhurst, E. Tran, A. Pasetto, P. Robbins et al., Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients, Nature Medicine, vol.22, issue.4, pp.433-441, 2016.
DOI : 10.4049/jimmunol.1103020

J. Wolchok, A. Hoos, O. Day, S. Weber, J. Hamid et al., Guidelines for the Evaluation of Immune Therapy Activity in Solid Tumors: Immune-Related Response Criteria, Clinical Cancer Research, vol.15, issue.23, pp.7412-7432, 2009.
DOI : 10.1158/1078-0432.CCR-09-1624

K. Wistuba-hamprecht, G. Pawelec, and E. Derhovanessian, OMIP-020: Phenotypic characterization of human ???? T-cells by multicolor flow cytometry, Cytometry Part A, vol.104, issue.6, pp.522-526, 2014.
DOI : 10.1182/blood-2004-01-0331

URL : http://onlinelibrary.wiley.com/doi/10.1002/cyto.a.22470/pdf

C. Balch, J. Gershenwald, S. Soong, J. Thompson, M. Atkins et al., Final Version of 2009 AJCC Melanoma Staging and Classification, Journal of Clinical Oncology, vol.27, issue.36, pp.6199-206, 2009.
DOI : 10.1200/JCO.2009.23.4799

URL : http://europepmc.org/articles/pmc2793035?pdf=render

P. Romero, A. Zippelius, I. Kurth, M. Pittet, C. Touvrey et al., Four Functionally Distinct Populations of Human Effector-Memory CD8+ T Lymphocytes, The Journal of Immunology, vol.178, issue.7, pp.4112-4121, 2007.
DOI : 10.4049/jimmunol.178.7.4112

URL : http://www.jimmunol.org/content/jimmunol/178/7/4112.full.pdf

A. Martens, K. Wistuba-hamprecht, M. Foppen, J. Yuan, M. Postow et al., Baseline Peripheral Blood Biomarkers Associated with Clinical Outcome of Advanced Melanoma Patients Treated with Ipilimumab, Clinical Cancer Research, vol.22, issue.12, pp.2908-2926, 2016.
DOI : 10.1158/1078-0432.CCR-15-2412

URL : https://hal.archives-ouvertes.fr/inserm-01409624

K. Wistuba-hamprecht, A. Martens, K. Haehnel, G. Foppen, M. Yuan et al., Proportions of blood-borne V??1+ and V??2+ T-cells are associated with overall survival of melanoma patients treated with ipilimumab, European Journal of Cancer, vol.64, pp.116-142, 2016.
DOI : 10.1016/j.ejca.2016.06.001

P. Kvistborg, D. Philips, S. Kelderman, L. Hageman, C. Ottensmeier et al., Anti-CTLA-4 therapy broadens the melanoma-reactive CD8þ T cell response, Sci Transl Med, vol.6, issue.254, pp.254-128, 2014.
DOI : 10.1126/scitranslmed.3008918

E. Van-allen, D. Miao, B. Schilling, S. Shukla, C. Blank et al., Genomic correlates of response to CTLA-4 blockade in metastatic melanoma PD-1 expression conditions T cell avidity within an antigen-specific repertoire, Science Oncoimmunology, vol.3505, issue.62571, pp.207-218, 2015.

I. Mullins, C. Slingluff, J. Lee, C. Garbee, J. Shu et al., T cells Is Associated with Survival in Melanoma Patients with Stage III Disease, Cancer Research, vol.64, issue.21, pp.7697-701, 2004.
DOI : 10.1158/0008-5472.CAN-04-2059

N. Jacquelot, D. Enot, C. Flament, N. Vimond, C. Blattner et al., Chemokine receptor patterns in lymphocytes mirror metastatic spreading in melanoma, Journal of Clinical Investigation, vol.126, issue.3, pp.921-958, 2016.
DOI : 10.1172/JCI80071DS1

URL : https://hal.archives-ouvertes.fr/hal-01295136

A. Bally, J. Austin, and J. Boss, Genetic and Epigenetic Regulation of PD-1 Expression, The Journal of Immunology, vol.5, issue.3, pp.2431-2438, 2016.
DOI : 10.1038/ni1046

URL : http://www.jimmunol.org/content/jimmunol/196/6/2431.full.pdf

N. Mcgranahan, A. Furness, R. Rosenthal, S. Ramskov, R. Lyngaa et al., Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade, Science, vol.7, issue.5, pp.1463-1472, 2016.
DOI : 10.1038/nprot.2012.037