Ipilimumab reshapes T cell memory subsets in melanoma patients with clinical response

被引:26
作者
Felix, Joana [1 ,2 ]
Lambert, Jerome [2 ,3 ,4 ]
Roelens, Marie [1 ]
Maubec, Eve [5 ]
Guermouche, Helene [1 ]
Pages, Cecile [6 ]
Sidina, Irina [6 ]
Cordeiro, Debora J. [1 ,2 ,7 ]
Maki, Guitta [7 ]
Chasset, Francois [6 ]
Porcher, Raphael [4 ,8 ,9 ]
Bagot, Martine [2 ,6 ,10 ]
Caignard, Anne [1 ]
Toubert, Antoine [1 ,2 ,7 ]
Lebbe, Celeste [2 ,6 ,10 ]
Moins-Teisserenc, Helene [1 ,2 ,7 ]
机构
[1] INSERM, Inst Univ Hematol, UMR 1160, Paris, France
[2] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France
[3] Hop St Louis, AP HP, Serv Biostat & Informat Med, Paris, France
[4] INSERM, UMR 1153, Ctr Rech Epidemiol & Stat CRESS, Paris, France
[5] Hop Xavier Bichat, AP HP, Serv Dermatol, Paris, France
[6] Hop St Louis, AP HP, Serv Dermatol, Paris, France
[7] Hop St Louis, AP HP, Lab Immunol Histocompatibil, Paris, France
[8] Hop Hotel Dieu, AP HP, Ctr Epidemiol Clin, Paris, France
[9] Univ Paris 05, Sorbonne Paris Cite, Paris, France
[10] Hop St Louis, INSERM, UMR 976, Paris, France
关键词
CTLA-4; immunotherapy; ipilimumab; melanoma; memory T cells; TSCM; LONG-TERM SURVIVAL; METASTATIC MELANOMA; CTLA-4; BLOCKADE; UNTREATED MELANOMA; ANTIGEN-4; EFFECTOR; IMMUNOTHERAPY; LYMPHOCYTE; EOMESODERMIN; DIFFERENTIATION;
D O I
10.1080/2162402X.2015.1136045
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: Therapy targeting CTLA-4 immune checkpoint provides increased survival in patients with advanced melanoma. However, immunotherapy is frequently associated with delayed and heterogeneous clinical responses and it is important to identify prognostic immunological correlates of clinical endpoints. Experimental design: 77 patients with stage III/IV melanoma were treated with ipilimumab alone every 3 weeks, during 9 weeks. Blood samples were collected at the baseline and before each dose for in depth immune monitoring. Results: The median follow-up was 28 mo with a median survival of 7 mo. Survival and clinical benefit were significantly improved when absolute lymphocyte count at the baseline was above 1 x 10(9)/L. Notably, ipilimumab had a global effect on memory T cells, with an early increase of central and effector subsets in patients with disease control. By contrast, percentages of stem cell memory T cells (TSCM) gradually decreased despite stable absolute counts and sustained proliferation, suggesting a process of differentiation. Higher proportions of eomes(+) and Ki-67(+) T cells were observed, with enhanced skin homing potential and induction of cytotoxic markers. Conclusion: These results suggest that CTLA-4 blockade is able to reshape the memory subset with the potential involvement of Eomes and memory subsets including TSCM.
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页数:10
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共 57 条
[1]   Final Version of 2009 AJCC Melanoma Staging and Classification [J].
Balch, Charles M. ;
Gershenwald, Jeffrey E. ;
Soong, Seng-jaw ;
Thompson, John F. ;
Atkins, Michael B. ;
Byrd, David R. ;
Buzaid, Antonio C. ;
Cochran, Alistair J. ;
Coit, Daniel G. ;
Ding, Shouluan ;
Eggermont, Alexander M. ;
Flaherty, Keith T. ;
Gimotty, Phyllis A. ;
Kirkwood, John M. ;
McMasters, Kelly M. ;
Mihm, Martin C., Jr. ;
Morton, Donald L. ;
Ross, Merrick I. ;
Sober, Arthur J. ;
Sondak, Vernon K. .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (36) :6199-6206
[2]   ICOS controls the pool size of effector-memory and regulatory T cells [J].
Burmeister, Yvonne ;
Lischke, Timo ;
Dahler, Anja C. ;
Mages, Hans Werner ;
Lam, Kong-Peng ;
Coyle, Anthony J. ;
Kroczek, Richard A. ;
Hutloff, Andreas .
JOURNAL OF IMMUNOLOGY, 2008, 180 (02) :774-782
[3]   Anti-CTLA-4 Antibody Therapy: Immune Monitoring During Clinical Development of a Novel Immunotherapy [J].
Callahan, Margaret K. ;
Wolchok, Jedd D. ;
Allison, James P. .
SEMINARS IN ONCOLOGY, 2010, 37 (05) :473-484
[4]   Preoperative CTLA-4 Blockade: Tolerability and Immune Monitoring in the Setting of a Presurgical Clinical Trial [J].
Carthon, Bradley C. ;
Wolchok, Jedd D. ;
Yuan, Jianda ;
Kamat, Ashish ;
Tang, Derek S. Ng ;
Sun, Jingjing ;
Ku, Geoffrey ;
Troncoso, Patricia ;
Logothetis, Christopher J. ;
Allison, James P. ;
Sharma, Padmanee .
CLINICAL CANCER RESEARCH, 2010, 16 (10) :2861-2871
[5]   Single-center study under a French Temporary Authorization for Use (TAU) protocol for ipilimumab in metastatic melanoma: negative impact of baseline corticosteroids [J].
Chasset, Francois ;
Pages, Cecile ;
Biard, Lucie ;
Roux, Jennifer ;
Sidina, Irina ;
Madelaine, Isabelle ;
Basset-Seguin, Nicole ;
Viguier, Manuelle ;
Madjlessi-Ezra, Nika ;
Schneider, Pierre ;
Bagot, Martine ;
Resche-Rigon, Matthieu ;
Lebbe, Celeste .
EUROPEAN JOURNAL OF DERMATOLOGY, 2015, 25 (01) :36-44
[6]   Detailed analysis of immunologic effects of the cytotoxic T lymphocyte-associated antigen 4-blocking monoclonal antibody tremelimumab in peripheral blood of patients with melanoma [J].
Comin-Anduix, Begona ;
Lee, Yohan ;
Jalil, Jason ;
Algazi, Alain ;
de la Rocha, Pilar ;
Camacho, Luis H. ;
Bozon, Viviana A. ;
Bulanhagui, Cecile A. ;
Seja, Elisabeth ;
Villanueva, Arturo ;
Straatsma, Bradley R. ;
Gualberto, Antonio ;
Economou, James S. ;
Glaspy, John A. ;
Gomez-Navarro, Jesus ;
Ribas, Antoni .
JOURNAL OF TRANSLATIONAL MEDICINE, 2008, 6 (1)
[7]   Combination Therapy with Anti-CTLA-4 and Anti-PD-1 Leads to Distinct Immunologic Changes In Vivo [J].
Das, Rituparna ;
Verma, Rakesh ;
Sznol, Mario ;
Boddupalli, Chandra Sekhar ;
Gettinger, Scott N. ;
Kluger, Harriet ;
Callahan, Margaret ;
Wolchok, Jedd D. ;
Halaban, Ruth ;
Dhodapkar, Madhav V. ;
Dhodapkar, Kavita M. .
JOURNAL OF IMMUNOLOGY, 2015, 194 (03) :950-959
[8]   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 [J].
Delyon, J. ;
Mateus, C. ;
Lefeuvre, D. ;
Lanoy, E. ;
Zitvogel, L. ;
Chaput, N. ;
Roy, S. ;
Eggermont, A. M. M. ;
Routier, E. ;
Robert, C. .
ANNALS OF ONCOLOGY, 2013, 24 (06) :1697-1703
[9]   Ipilimumab experience in heavily pretreated patients with melanoma in an expanded access program at the University Hospital of Siena (Italy) [J].
Di Giacomo, Anna Maria ;
Danielli, Riccardo ;
Calabro, Luana ;
Bertocci, Erica ;
Nannicini, Chiara ;
Giannarelli, Diana ;
Balestrazzi, Angelo ;
Vigni, Francesco ;
Riversi, Valentina ;
Miracco, Clelia ;
Biagioli, Maurizio ;
Altomonte, Maresa ;
Maio, Michele .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2011, 60 (04) :467-477
[10]   Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-associated antigen-4 blockade [J].
Downey, Stephanie G. ;
Klapper, Jacob A. ;
Smith, Franz O. ;
Yang, James C. ;
Sherry, Richard M. ;
Royal, Richard E. ;
Kammula, Udai S. ;
Hughes, Marybeth S. ;
Allen, Tamika E. ;
Levy, Catherine L. ;
Yellin, Michael ;
Nich, Geoffrey ;
White, Donald E. ;
Steinberg, Seth M. ;
Rosenberg, Steven A. .
CLINICAL CANCER RESEARCH, 2007, 13 (22) :6681-6688