One particular paradigm of anticancer immunotherapy relies on the administration of (potentially) tumor-reactive immune effector cells. Generally, these cells are obtained from autologous peripheral blood lymphocytes (PBLs) ex vivo (in the context of appropriate expansion, activation and targeting protocols), and re-infused into lymphodepleted patients along with immunostimulatory agents. In spite of the consistent progress achieved throughout the past two decades in this field, no adoptive cell transfer (ACT)-based immunotherapeutic regimen is currently approved by regulatory agencies for use in cancer patients. Nonetheless, the interest of oncologists in ACT-based immunotherapy continues to increase. Accumulating clinical evidence indicates indeed that specific paradigms of ACT, such as the infusion of chimeric antigen receptor (CAR)-expressing autologous T cells, are associated with elevated rates of durable responses in patients affected by various neoplasms. In line with this notion, clinical trials investigating the safety and therapeutic activity of ACT in cancer patients are being initiated at an ever increasing pace. Here, we review recent preclinical and clinical advances in the development of ACT-based immunotherapy for oncological indications.

Group of Immune Receptors of the Innate and Adaptive System; Institut d'Investigacions Biomédiques August Pi i Sunyer ; Barcelona Spain

Gustave Roussy Cancer Campus ; Villejuif France

Gustave Roussy Cancer Campus ; Villejuif France ; INSERM; U1015; CICBT507 ; Villejuif France

Gustave Roussy Cancer Campus ; Villejuif France ; INSERM; U1138 ; Paris France ; Equipe 11 labellisée par la Ligue Nationale contre le Cancer; Centre de Recherche des Cordeliers ; Paris France

Gustave Roussy Cancer Campus ; Villejuif France ; INSERM; U1138 ; Paris France ; Equipe 11 labellisée par la Ligue Nationale contre le Cancer; Centre de Recherche des Cordeliers ; Paris France ; Université Pierre et Marie Curie Paris 6 ; Paris France ; Université Paris Descartes Paris 5 Sorbonne Paris Cité Paris France

INSERM; U1138 ; Paris France ; Equipe 11 labellisée par la Ligue Nationale contre le Cancer; Centre de Recherche des Cordeliers ; Paris France ; Faculté de Medicine; Université Paris Sud Paris XI ; Le Kremlin Bicêtre France ; Sotio a c ; Prague Czech Republic

INSERM; U1138 ; Paris France ; Equipe 11 labellisée par la Ligue Nationale contre le Cancer; Centre de Recherche des Cordeliers ; Paris France ; Université Pierre et Marie Curie Paris 6 ; Paris France ; Université Paris Descartes Paris 5 Sorbonne Paris Cité Paris France ; Pôle de Biologie; Hôpital Européen Georges Pompidou; AP HP ; Paris France ; Metabolomics and Cell Biology Platforms; Gustave Roussy Cancer Campus ; Villejuif France

INSERM; U1138 ; Paris France ; Equipe 13; Centre de Recherche des Cordeliers ; Paris France ; Université Pierre et Marie Curie Paris 6 ; Paris France

INSERM; U1138 ; Paris France ; Université Pierre et Marie Curie Paris 6 ; Paris France ; Laboratory of Integrative Cancer Immunology; Centre de Recherche des Cordeliers ; Paris France ; Université Paris Descartes Paris 5 Sorbonne Paris Cité Paris France

Sotio a c ; Prague Czech Republic ; Dept of Immunology; 2nd Faculty of Medicine and University Hospital Motol; Charles University ; Prague Czech Republic

Université Paris Descartes Paris 5 Sorbonne Paris Cité Paris France ; INSERM; U970 ; Paris France ; Paris Cardiovascular Research Center ; AP HP ; Paris France

Zobrazit více v PubMed

Rosenberg SA, Restifo NP. Adoptive cell transfer as personalized immunotherapy for human cancer. Science 2015; 348:62-8; PMID:25838374; http://dx.doi.org/10.1126/science.aaa4967 PubMed DOI PMC

June CH, Riddell SR, Schumacher TN. Adoptive cellular therapy: a race to the finish line. Sci Transl Med 2015; 7:280ps7; PMID:25810311; http://dx.doi.org/10.1126/scitranslmed.aaa3643 PubMed DOI

Bluestone JA, Tang Q. Immunotherapy: making the case for precision medicine. Sci Transl Med 2015; 7:280ed3; PMID:25810308; http://dx.doi.org/10.1126/scitranslmed.aaa9846 PubMed DOI

Restifo NP, Dudley ME, Rosenberg SA. Adoptive immunotherapy for cancer: harnessing the T cell response. Nat Rev Immunol 2012; 12:269-81; PMID:22437939; http://dx.doi.org/10.1038/nri3191 PubMed DOI PMC

Rosenberg SA. Cell transfer immunotherapy for metastatic solid cancer–what clinicians need to know. Nat Rev Clin Oncol 2011; 8:577-85; PMID:21808266; http://dx.doi.org/10.1038/nrclinonc.2011.116 PubMed DOI PMC

Rosenberg SA, Restifo NP, Yang JC, Morgan RA, Dudley ME. Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer 2008; 8:299-308; PMID:18354418; http://dx.doi.org/10.1038/nrc2355 PubMed DOI PMC

Kirk R. Immunotherapy: adoptive cell therapy simplified. Nat Rev Clin Oncol 2013; 10:368; PMID:23689751; http://dx.doi.org/10.1038/nrclinonc.2013.85 PubMed DOI

Humphries C. Adoptive cell therapy: honing that killer instinct. Nature 2013; 504:S13-5; PMID:24352359; http://dx.doi.org/10.1038/504S13a PubMed DOI

Maus MV, Fraietta JA, Levine BL, Kalos M, Zhao Y, June CH. Adoptive immunotherapy for cancer or viruses. Annu Rev Immunol 2014; 32:189-225; PMID:24423116; http://dx.doi.org/10.1146/annurev-immunol-032713-120136 PubMed DOI PMC

Jenq RR, van den Brink MR. Allogeneic haematopoietic stem cell transplantation: individualized stem cell and immune therapy of cancer. Nat Rev Cancer 2010; 10:213-21; PMID:20168320; http://dx.doi.org/10.1038/nrc2804 PubMed DOI

Barriga F, Ramirez P, Wietstruck A, Rojas N. Hematopoietic stem cell transplantation: clinical use and perspectives. Biol Res 2012; 45:307-16; PMID:23283440; http://dx.doi.org/10.4067/S0716-97602012000300012 PubMed DOI

McDonald-Hyman C, Turka LA, Blazar BR. Advances and challenges in immunotherapy for solid organ and hematopoietic stem cell transplantation. Sci Transl Med 2015; 7:280rv2; PMID:25810312; http://dx.doi.org/10.1126/scitranslmed.aaa6853 PubMed DOI PMC

Galluzzi L, Senovilla L, Vacchelli E, Eggermont A, Fridman WH, Galon J, Sautès-Fridman C, Tartour E, Zitvogel L, Kroemer G. Trial watch: dendritic cell-based interventions for cancer therapy. Oncoimmunology 2012; 1:1111-34; PMID:23170259; http://dx.doi.org/10.4161/onci.21494 PubMed DOI PMC

Vacchelli E, Vitale I, Eggermont A, Fridman WH, Fucikova J, Cremer I, Galon J, Tartour E, Zitvogel L, Kroemer G et al.. Trial watch: dendritic cell-based interventions for cancer therapy. Oncoimmunology 2013; 2:e25771; PMID:24286020; http://dx.doi.org/10.4161/onci.25771 PubMed DOI PMC

Palucka K, Banchereau J. Cancer immunotherapy via dendritic cells. Nat Rev Cancer 2012; 12:265-77; PMID:22437871; http://dx.doi.org/10.1038/nrc3258 PubMed DOI PMC

Palucka K, Banchereau J. Dendritic-cell-based therapeutic cancer vaccines. Immunity 2013; 39:38-48; PMID:23890062; http://dx.doi.org/10.1016/j.immuni.2013.07.004 PubMed DOI PMC

Galluzzi L, Vacchelli E, Bravo-San Pedro JM, Buque A, Senovilla L, Baracco EE, Bloy N, Castoldi F, Abastado JP, Agostinis P et al.. Classification of current anticancer immunotherapies. Oncotarget 2014; 5:12472-508; PMID:25537519 PubMed PMC

Pages F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R, Mlecnik B, Kirilovsky A, Nilsson M, Damotte D et al.. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med 2005; 353:2654-66; PMID:16371631; http://dx.doi.org/10.1056/NEJMoa051424 PubMed DOI

Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P et al.. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006; 313:1960-4; PMID:17008531; http://dx.doi.org/10.1126/science.1129139 PubMed DOI

Mlecnik B, Tosolini M, Kirilovsky A, Berger A, Bindea G, Meatchi T, Bruneval P, Trajanoski Z, Fridman WH, Pagès F et al.. Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol 2011; 29:610-8; PMID:21245428; http://dx.doi.org/10.1200/JCO.2010.30.5425 PubMed DOI

Galon J, Angell HK, Bedognetti D, Marincola FM. The continuum of cancer immunosurveillance: prognostic, predictive, and mechanistic signatures. Immunity 2013; 39:11-26; PMID:23890060; http://dx.doi.org/10.1016/j.immuni.2013.07.008 PubMed DOI

Bindea G, Mlecnik B, Tosolini M, Kirilovsky A, Waldner M, Obenauf AC, Angell H, Fredriksen T, Lafontaine L, Berger A et al.. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity 2013; 39:782-95; PMID:24138885; http://dx.doi.org/10.1016/j.immuni.2013.10.003 PubMed DOI

Galon J, Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C, Lugli A, Zlobec I, Hartmann A, Bifulco C et al.. Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours. J Pathol 2014; 232:199-209; PMID:24122236; http://dx.doi.org/10.1002/path.4287 PubMed DOI PMC

Yun YS, Hargrove ME, Ting CC. In vivo antitumor activity of anti-CD3-induced activated killer cells. Cancer Res 1989; 49:4770-4; PMID:2527087 PubMed

Bouquie R, Bonnin A, Bernardeau K, Khammari A, Dreno B, Jotereau F, Labarrière N, Lang F. A fast and efficient HLA multimer-based sorting procedure that induces little apoptosis to isolate clinical grade human tumor specific T lymphocytes. Cancer Immunol Immunother 2009; 58:553-66; PMID:18751701; http://dx.doi.org/10.1007/s00262-008-0578-2 PubMed DOI PMC

Chacon JA, Pilon-Thomas S, Sarnaik AA, Radvanyi LG. Continuous 4-1BB co-stimulatory signals for the optimal expansion of tumor-infiltrating lymphocytes for adoptive T-cell therapy. Oncoimmunology 2013; 2:e25581; PMID:24319633; http://dx.doi.org/10.4161/onci.25581 PubMed DOI PMC

Chhabra A, Yang L, Wang P, Comin-Anduix B, Das R, Chakraborty NG, Ray S, Mehrotra S, Yang H, Hardee CL et al.. CD4+CD25- T cells transduced to express MHC class I-restricted epitope-specific TCR synthesize Th1 cytokines and exhibit MHC class I-restricted cytolytic effector function in a human melanoma model. J Immunol 2008; 181:1063-70; PMID:18606658; http://dx.doi.org/10.4049/jimmunol.181.2.1063 PubMed DOI PMC

Ray S, Chhabra A, Chakraborty NG, Hegde U, Dorsky DI, Chodon T, von Euw E, Comin-Anduix B, Koya RC, Ribas A et al.. MHC-I-restricted melanoma antigen specific TCR-engineered human CD4+ T cells exhibit multifunctional effector and helper responses, in vitro. Clin Immunol 2010; 136:338-47; PMID:20547105; http://dx.doi.org/10.1016/j.clim.2010.04.013 PubMed DOI PMC

Sadelain M, Riviere I, Brentjens R. Targeting tumours with genetically enhanced T lymphocytes. Nat Rev Cancer 2003; 3:35-45; PMID:12509765; http://dx.doi.org/10.1038/nrc971 PubMed DOI

Robbins PF, Morgan RA, Feldman SA, Yang JC, Sherry RM, Dudley ME, Wunderlich JR, Nahvi AV, Helman LJ, Mackall CL et al.. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol 2011; 29:917-24; PMID:21282551; http://dx.doi.org/10.1200/JCO.2010.32.2537 PubMed DOI PMC

Sadelain M, Brentjens R, Riviere I. The basic principles of chimeric antigen receptor design. Cancer Discov 2013; 3:388-98; PMID:23550147; http://dx.doi.org/10.1158/2159-8290.CD-12-0548 PubMed DOI PMC

Dotti G, Gottschalk S, Savoldo B, Brenner MK. Design and development of therapies using chimeric antigen receptor-expressing T cells. Immunol Rev 2014; 257:107-26; PMID:24329793; http://dx.doi.org/10.1111/imr.12131 PubMed DOI PMC

Jensen MC, Riddell SR. Design and implementation of adoptive therapy with chimeric antigen receptor-modified T cells. Immunol Rev 2014; 257:127-44; PMID:24329794; http://dx.doi.org/10.1111/imr.12139 PubMed DOI PMC

Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med 2011; 365:725-33; PMID:21830940; http://dx.doi.org/10.1056/NEJMoa1103849 PubMed DOI PMC

Kochenderfer JN, Rosenberg SA. Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors. Nat Rev Clin Oncol 2013; 10:267-76; PMID:23546520; http://dx.doi.org/10.1038/nrclinonc.2013.46 PubMed DOI PMC

Long AH, Haso WM, Orentas RJ. Lessons learned from a highly-active CD22-specific chimeric antigen receptor. Oncoimmunology 2013; 2:e23621; PMID:23734316; http://dx.doi.org/10.4161/onci.23621 PubMed DOI PMC

Spear P, Barber A, Sentman CL. Collaboration of chimeric antigen receptor (CAR)-expressing T cells and host T cells for optimal elimination of established ovarian tumors. Oncoimmunology 2013; 2:e23564; PMID:23734311; http://dx.doi.org/10.4161/onci.23564 PubMed DOI PMC

Kochenderfer JN, Dudley ME, Feldman SA, Wilson WH, Spaner DE, Maric I, Stetler-Stevenson M, Phan GQ, Hughes MS, Sherry RM et al.. B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood 2012; 119:2709-20; PMID:22160384; http://dx.doi.org/10.1182/blood-2011-10-384388 PubMed DOI PMC

Kochenderfer JN, Wilson WH, Janik JE, Dudley ME, Stetler-Stevenson M, Feldman SA, Maric I, Raffeld M, Nathan DA, Lanier BJ et al.. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood 2010; 116:4099-102; PMID:20668228; http://dx.doi.org/10.1182/blood-2010-04-281931 PubMed DOI PMC

Kochenderfer JN, Yu Z, Frasheri D, Restifo NP, Rosenberg SA. Adoptive transfer of syngeneic T cells transduced with a chimeric antigen receptor that recognizes murine CD19 can eradicate lymphoma and normal B cells. Blood 2010; 116:3875-86; PMID:20631379; http://dx.doi.org/10.1182/blood-2010-01-265041 PubMed DOI PMC

Brentjens RJ, Riviere I, Park JH, Davila ML, Wang X, Stefanski J, Taylor C, Yeh R, Bartido S, Borquez-Ojeda O et al.. Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood 2011; 118:4817-28; PMID:21849486; http://dx.doi.org/10.1182/blood-2011-04-348540 PubMed DOI PMC

Kalos M, Levine BL, Porter DL, Katz S, Grupp SA, Bagg A, June CH. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med 2011; 3:95ra73; PMID:21832238; http://dx.doi.org/10.1126/scitranslmed.3002842 PubMed DOI PMC

Savoldo B, Ramos CA, Liu E, Mims MP, Keating MJ, Carrum G, Kamble RT, Bollard CM, Gee AP, Mei Z et al.. CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. J Clin Invest 2011; 121:1822-6; PMID:21540550; http://dx.doi.org/10.1172/JCI46110 PubMed DOI PMC

Brentjens RJ, Davila ML, Riviere I, Park J, Wang X, Cowell LG, Bartido S, Stefanski J, Taylor C, Olszewska M et al.. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med 2013; 5:177ra38; PMID:23515080; http://dx.doi.org/10.1126/scitranslmed.3005930 PubMed DOI PMC

Gruber T, Hinterleitner R, Pfeifhofer-Obermair C, Wolf D, Baier G. Engineering effective T-cell based antitumor immunity. Oncoimmunology 2013; 2:e22893; PMID:23525844; http://dx.doi.org/10.4161/onci.22893 PubMed DOI PMC

Merhavi-Shoham E, Haga-Friedman A, Cohen CJ. Genetically modulating T-cell function to target cancer. Semin Cancer Biol 2012; 22:14-22; PMID:22210183; http://dx.doi.org/10.1016/j.semcancer.2011.12.006 PubMed DOI

Liu K, Rosenberg SA. Transduction of an IL-2 gene into human melanoma-reactive lymphocytes results in their continued growth in the absence of exogenous IL-2 and maintenance of specific antitumor activity. J Immunol 2001; 167:6356-65; PMID:11714800; http://dx.doi.org/10.4049/jimmunol.167.11.6356 PubMed DOI PMC

Zhou J, Shen X, Huang J, Hodes RJ, Rosenberg SA, Robbins PF. Telomere length of transferred lymphocytes correlates with in vivo persistence and tumor regression in melanoma patients receiving cell transfer therapy. J Immunol 2005; 175:7046-52; PMID:16272366; http://dx.doi.org/10.4049/jimmunol.175.10.7046 PubMed DOI PMC

Kalbasi A, Shrimali RK, Chinnasamy D, Rosenberg SA. Prevention of interleukin-2 withdrawal-induced apoptosis in lymphocytes retrovirally cotransduced with genes encoding an antitumor T-cell receptor and an antiapoptotic protein. J Immunother 2010; 33:672-83; PMID:20664359; http://dx.doi.org/10.1097/CJI.0b013e3181e475cd PubMed DOI PMC

Kershaw MH, Teng MW, Smyth MJ, Darcy PK. Supernatural T cells: genetic modification of T cells for cancer therapy. Nat Rev Immunol 2005; 5:928-40; PMID:16322746; http://dx.doi.org/10.1038/nri1729 PubMed DOI

Brennen WN, Drake CG, Isaacs JT. Enhancement of the T-cell armamentarium as a cell-based therapy for prostate cancer. Cancer Res 2014; 74:3390-5; PMID:24747912; http://dx.doi.org/10.1158/0008-5472.CAN-14-0249 PubMed DOI PMC

Hinrichs CS, Borman ZA, Gattinoni L, Yu Z, Burns WR, Huang J, Klebanoff CA, Johnson LA, Kerkar SP, Yang S et al.. Human effector CD8+ T cells derived from naive rather than memory subsets possess superior traits for adoptive immunotherapy. Blood 2011; 117:808-14; PMID:20971955; http://dx.doi.org/10.1182/blood-2010-05-286286 PubMed DOI PMC

Bellone M, Calcinotto A, Corti A. Won't you come on in? How to favor lymphocyte infiltration in tumors. Oncoimmunology 2012; 1:986-8; PMID:23162781; http://dx.doi.org/10.4161/onci.20213 PubMed DOI PMC

Cieri N, Camisa B, Cocchiarella F, Forcato M, Oliveira G, Provasi E, Bondanza A, Bordignon C, Peccatori J, Ciceri F et al.. IL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors. Blood 2013; 121:573-84; PMID:23160470; http://dx.doi.org/10.1182/blood-2012-05-431718 PubMed DOI

Gattinoni L, Klebanoff CA, Restifo NP. Paths to stemness: building the ultimate antitumour T cell. Nat Rev Cancer 2012; 12:671-84; PMID:22996603; http://dx.doi.org/10.1038/nrc3322 PubMed DOI PMC

Lugli E, Dominguez MH, Gattinoni L, Chattopadhyay PK, Bolton DL, Song K, Klatt NR, Brenchley JM, Vaccari M, Gostick q et al.. Superior T memory stem cell persistence supports long-lived T cell memory. J Clin Invest 2013; 123(2):594-9; PMID:23281401; http://dx.doi.org/10.1172/JCI66327 PubMed DOI PMC

Gattinoni L, Lugli E, Ji Y, Pos Z, Paulos CM, Quigley MF, Almeida JR, Gostick E, Yu Z, Carpenito C et al.. A human memory T cell subset with stem cell-like properties. Nat Med 2011; 17:1290-7; PMID:21926977; http://dx.doi.org/10.1038/nm.2446 PubMed DOI PMC

Galluzzi L, Lugli E. Rejuvenated T cells attack old tumors. Oncoimmunology 2013; 2:e24103; PMID:23526137; http://dx.doi.org/10.4161/onci.24103 PubMed DOI PMC

Somerville RP, Dudley ME. Bioreactors get personal. Oncoimmunology 2012; 1:1435-7; PMID:23243620; http://dx.doi.org/10.4161/onci.21206 PubMed DOI PMC

Wrzesinski C, Paulos CM, Kaiser A, Muranski P, Palmer DC, Gattinoni L, Yu Z, Rosenberg SA, Restifo NP. Increased intensity lymphodepletion enhances tumor treatment efficacy of adoptively transferred tumor-specific T cells. J Immunother 2010; 33:1-7; PMID:19952961; http://dx.doi.org/10.1097/CJI.0b013e3181b88ffc PubMed DOI PMC

Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 2009; 9:162-74; PMID:19197294; http://dx.doi.org/10.1038/nri2506 PubMed DOI PMC

Montero AJ, Diaz-Montero CM, Kyriakopoulos CE, Bronte V, Mandruzzato S. Myeloid-derived suppressor cells in cancer patients: a clinical perspective. J Immunother 2012; 35:107-15; PMID:22306898; http://dx.doi.org/10.1097/CJI.0b013e318242169f PubMed DOI

Nagaraj S, Gabrilovich DI. Myeloid-derived suppressor cells in human cancer. Cancer J 2010; 16:348-53; PMID:20693846; http://dx.doi.org/10.1097/PPO.0b013e3181eb3358 PubMed DOI

Cheng G, Yu A, Malek TR. T-cell tolerance and the multi-functional role of IL-2R signaling in T-regulatory cells. Immunol Rev 2011; 241:63-76; PMID:21488890; http://dx.doi.org/10.1111/j.1600-065X.2011.01004.x PubMed DOI PMC

Rudensky AY. Regulatory T cells and Foxp3. Immunol Rev 2011; 241:260-8; PMID:21488902; http://dx.doi.org/10.1111/j.1600-065X.2011.01018.x PubMed DOI PMC

Yao X, Ahmadzadeh M, Lu YC, Liewehr DJ, Dudley ME, Liu F, Schrump DS, Steinberg SM, Rosenberg SA, Robbins PF. Levels of peripheral CD4(+)FoxP3(+) regulatory T cells are negatively associated with clinical response to adoptive immunotherapy of human cancer. Blood 2012; 119:5688-96; PMID:22555974; http://dx.doi.org/10.1182/blood-2011-10-386482 PubMed DOI PMC

Kodumudi KN, Weber A, Sarnaik AA, Pilon-Thomas S. Blockade of myeloid-derived suppressor cells after induction of lymphopenia improves adoptive T cell therapy in a murine model of melanoma. J Immunol 2012; 189:5147-54; PMID:23100512; http://dx.doi.org/10.4049/jimmunol.1200274 PubMed DOI PMC

Pere H, Tanchot C, Bayry J, Terme M, Taieb J, Badoual C, Adotevi O, Merillon N, Marcheteau E, Quillien VR et al.. Comprehensive analysis of current approaches to inhibit regulatory T cells in cancer. Oncoimmunology 2012; 1:326-33; PMID:22737608; http://dx.doi.org/10.4161/onci.18852 PubMed DOI PMC

Senovilla L, Vitale I, Martins I, Tailler M, Pailleret C, Michaud M, Galluzzi L, Adjemian S, Kepp O, Niso-Santano M et al.. An immunosurveillance mechanism controls cancer cell ploidy. Science 2012; 337:1678-84; PMID:23019653; http://dx.doi.org/10.1126/science.1224922 PubMed DOI

Gattinoni L, Finkelstein SE, Klebanoff CA, Antony PA, Palmer DC, Spiess PJ, Hwang LN, Yu Z, Wrzesinski C, Heimann DM et al.. Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells. J Exp Med 2005; 202:907-12; PMID:16203864; http://dx.doi.org/10.1084/jem.20050732 PubMed DOI PMC

Klebanoff CA, Khong HT, Antony PA, Palmer DC, Restifo NP. Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy. Trends Immunol 2005; 26:111-7; PMID:15668127; http://dx.doi.org/10.1016/j.it.2004.12.003 PubMed DOI PMC

Vacchelli E, Eggermont A, Fridman WH, Galon J, Tartour E, Zitvogel L, Kroemer G, Galluzzi L. Trial Watch: adoptive cell transfer for anticancer immunotherapy. Oncoimmunology 2013; 2:e24238; PMID:23762803; http://dx.doi.org/10.4161/onci.24238 PubMed DOI PMC

Galluzzi L, Vacchelli E, Eggermont A, Fridman WH, Galon J, Sautes-Fridman C, Tartour E, Zitvogel L, Kroemer G. Trial Watch: adoptive cell transfer immunotherapy. Oncoimmunology 2012; 1:306-15; PMID:22737606; http://dx.doi.org/10.4161/onci.19549 PubMed DOI PMC

Alizadeh D, Trad M, Hanke NT, Larmonier CB, Janikashvili N, Bonnotte B, Katsanis E, Larmonier N. Doxorubicin eliminates myeloid-derived suppressor cells and enhances the efficacy of adoptive T-cell transfer in breast cancer. Cancer Res 2014; 74:104-18; PMID:24197130; http://dx.doi.org/10.1158/0008-5472.CAN-13-1545 PubMed DOI PMC

Mignot G, Ullrich E, Bonmort M, Menard C, Apetoh L, Taieb J, Bosisio D, Sozzani S, Ferrantini M, Schmitz J et al.. The critical role of IL-15 in the antitumor effects mediated by the combination therapy imatinib and IL-2. J Immunol 2008; 180:6477-83; PMID:18453565; http://dx.doi.org/10.4049/jimmunol.180.10.6477 PubMed DOI

Ullrich E, Bonmort M, Mignot G, Jacobs B, Bosisio D, Sozzani S, Jalil A, Louache F, Bulanova E, Geissman F et al.. Trans-presentation of IL-15 dictates IFN-producing killer dendritic cells effector functions. J Immunol 2008; 180:7887-97; PMID:18523252; http://dx.doi.org/10.4049/jimmunol.180.12.7887 PubMed DOI

Liu DL, Hakansson CH, Seifert J. Immunotherapy in liver tumors: II. Intratumoral injection with activated tumor-infiltrating lymphocytes, intrasplenic administration of recombinant interleukin-2 and interferon alpha causes tumor regression and lysis. Cancer Lett 1994; 85:39-46; PMID:7923100; http://dx.doi.org/10.1016/0304-3835(94)90236-4 PubMed DOI

Helms MW, Prescher JA, Cao YA, Schaffert S, Contag CH. IL-12 enhances efficacy and shortens enrichment time in cytokine-induced killer cell immunotherapy. Cancer Immunol Immunother 2010; 59:1325-34; PMID:20532883; http://dx.doi.org/10.1007/s00262-010-0860-y PubMed DOI PMC

Galluzzi L, Vacchelli E, Eggermont A, Fridman WH, Galon J, Sautes-Fridman C, Tartour E, Zitvogel L, Kroemer G. Trial Watch: Experimental Toll-like receptor agonists for cancer therapy. Oncoimmunology 2012; 1:699-716; PMID:22934262; http://dx.doi.org/10.4161/onci.20696 PubMed DOI PMC

Paulos CM, Kaiser A, Wrzesinski C, Hinrichs CS, Cassard L, Boni A, Muranski P, Sanchez-Perez L, Palmer DC, Yu Z et al.. Toll-like receptors in tumor immunotherapy. Clin Cancer Res 2007; 13:5280-9; PMID:17875756; http://dx.doi.org/10.1158/1078-0432.CCR-07-1378 PubMed DOI PMC

Vacchelli E, Galluzzi L, Eggermont A, Fridman WH, Galon J, Sautes-Fridman C, Tartour E, Zitvogel L, Kroemer G. Trial watch: FDA-approved Toll-like receptor agonists for cancer therapy. Oncoimmunology 2012; 1:894-907; PMID:23162757; http://dx.doi.org/10.4161/onci.20931 PubMed DOI PMC

Yang Y, Huang CT, Huang X, Pardoll DM. Persistent Toll-like receptor signals are required for reversal of regulatory T cell-mediated CD8 tolerance. Nat Immunol 2004; 5:508-15; PMID:15064759; http://dx.doi.org/10.1038/ni1059 PubMed DOI

Galluzzi L, Senovilla L, Zitvogel L, Kroemer G. The secret ally: immunostimulation by anticancer drugs. Nat Rev Drug Discov 2012; 11:215-33; PMID:22301798; http://dx.doi.org/10.1038/nrd3626 PubMed DOI

Zitvogel L, Galluzzi L, Smyth MJ, Kroemer G. Mechanism of action of conventional and targeted anticancer therapies: reinstating immunosurveillance. Immunity 2013; 39:74-88; PMID:23890065; http://dx.doi.org/10.1016/j.immuni.2013.06.014 PubMed DOI

Kan S, Hazama S, Maeda K, Inoue Y, Homma S, Koido S, Okamoto M, Oka M. Suppressive effects of cyclophosphamide and gemcitabine on regulatory T-cell induction in vitro. Anticancer Res 2012; 32:5363-9; PMID:23225438 PubMed

Tongu M, Harashima N, Monma H, Inao T, Yamada T, Kawauchi H, Harada M. Metronomic chemotherapy with low-dose cyclophosphamide plus gemcitabine can induce anti-tumor T cell immunity in vivo. Cancer Immunol Immunother 2013; 62:383-91; PMID:22926062; http://dx.doi.org/10.1007/s00262-012-1343-0 PubMed DOI PMC

Kepp O, Senovilla L, Vitale I, Vacchelli E, Adjemian S, Agostinis P, Apetoh L, Aranda F, Barnaba V, Bloy N et al.. Consensus guidelines for the detection of immunogenic cell death. Oncoimmunology 2014; 3: e955691; PMID:25941621; http://dx.doi.org/2356216110.4161/21624011.2014.9555691 PubMed DOI PMC

Ma Y, Adjemian S, Mattarollo SR, Yamazaki T, Aymeric L, Yang H, Portela Catani JP, Hannani D, Duret H, Steegh K et al.. Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cells. Immunity 2013; 38:729-41; PMID:23562161; http://dx.doi.org/10.1016/j.immuni.2013.03.003 PubMed DOI

Lee J, Park SH, Chang HM, Kim JS, Choi HJ, Lee MA, Jang JS, Jeung HC, Kang JH, Lee HW et al.. Gemcitabine and oxaliplatin with or without erlotinib in advanced biliary-tract cancer: a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 2012; 13:181-8; PMID:22192731; http://dx.doi.org/10.1016/S1470-2045(11)70301-1 PubMed DOI

Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN et al.. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013; 369:1691-703; PMID:24131140; http://dx.doi.org/10.1056/NEJMoa1304369 PubMed DOI PMC

Gujar SA, Clements D, Lee PW. Two is better than one: complementing oncolytic virotherapy with gemcitabine to potentiate antitumor immune responses. Oncoimmunology 2014; 3:e27622; PMID:24804161; http://dx.doi.org/10.4161/onci.27622 PubMed DOI PMC

Galluzzi L, Vitale I, Senovilla L, Olaussen KA, Pinna G, Eisenberg T, Goubar A, Martins I, Michels J, Kratassiouk G et al.. Prognostic impact of vitamin B6 metabolism in lung cancer. Cell Rep 2012; 2:257-69; PMID:22854025; http://dx.doi.org/10.1016/j.celrep.2012.06.017 PubMed DOI

Galluzzi L, Senovilla L, Vitale I, Michels J, Martins I, Kepp O, Castedo M, Kroemer G. Molecular mechanisms of cisplatin resistance. Oncogene 2012; 31:1869-83; PMID:21892204; http://dx.doi.org/10.1038/onc.2011.384 PubMed DOI

Michaud M, Martins I, Sukkurwala AQ, Adjemian S, Ma Y, Pellegatti P, Shen S, Kepp O, Scoazec M, Mignot G et al.. Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science 2011; 334:1573-7; PMID:22174255; http://dx.doi.org/10.1126/science.1208347 PubMed DOI

Peng W, Lizee G, Hwu P. Blockade of the PD-1 pathway enhances the efficacy of adoptive cell therapy against cancer. Oncoimmunology 2013; 2:e22691; PMID:23524510; http://dx.doi.org/10.4161/onci.22691 PubMed DOI PMC

Galluzzi L, Kroemer G, Eggermont A. Novel immune checkpoint blocker approved for the treatment of advanced melanoma. Oncoimmunology 2014; 3:e967147; PMID: 25941597; http://dx.doi.org/10.4161/21624011.2014.967147 PubMed DOI PMC

John LB, Kershaw MH, Darcy PK. Blockade of PD-1 immunosuppression boosts CAR T-cell therapy. Oncoimmunology 2013; 2:e26286; PMID:24353912; http://dx.doi.org/10.4161/onci.26286 PubMed DOI PMC

Dings RP, Vang KB, Castermans K, Popescu F, Zhang Y, Oude Egbrink MG, Mescher MF, Farrar MA, Griffioen AW, Mayo KH. Enhancement of T-cell-mediated antitumor response: angiostatic adjuvant to immunotherapy against cancer. Clin Cancer Res 2011; 17:3134-45; PMID:21252159; http://dx.doi.org/10.1158/1078-0432.CCR-10-2443 PubMed DOI PMC

Shrimali RK, Yu Z, Theoret MR, Chinnasamy D, Restifo NP, Rosenberg SA. Antiangiogenic agents can increase lymphocyte infiltration into tumor and enhance the effectiveness of adoptive immunotherapy of cancer. Cancer Res 2010; 70:6171-80; PMID:20631075; http://dx.doi.org/10.1158/0008-5472.CAN-10-0153 PubMed DOI PMC

Mok S, Koya RC, Tsui C, Xu J, Robert L, Wu L, Graeber TG, West BL, Bollag G, Ribas A. Inhibition of CSF-1 receptor improves the antitumor efficacy of adoptive cell transfer immunotherapy. Cancer Res 2014; 74:153-61; PMID:24247719; http://dx.doi.org/10.1158/0008-5472.CAN-13-1816 PubMed DOI PMC

Senovilla L, Aranda F, Galluzzi L, Kroemer G. Impact of myeloid cells on the efficacy of anticancer chemotherapy. Curr Opin Immunol 2014; 30C:24-31; PMID:24950501; http://dx.doi.org/10.1016/j.coi.2014.05.009 PubMed DOI

Senovilla L, Vacchelli E, Galon J, Adjemian S, Eggermont A, Fridman WH, Sautès-Fridman C, Ma Y, Tartour E, Zitvogel L et al.. Trial watch: prognostic and predictive value of the immune infiltrate in cancer. Oncoimmunology 2012; 1:1323-43; PMID:23243596; http://dx.doi.org/10.4161/onci.22009 PubMed DOI PMC

Ledford H. T-cell therapy extends cancer survival to years. Nature 2014; 516:156; PMID:25503214; http://dx.doi.org/10.1038/516156a PubMed DOI

Beatty GL. Engineered chimeric antigen receptor-expressing T cells for the treatment of pancreatic ductal adenocarcinoma. Oncoimmunology 2014; 3:e28327; PMID:25050204; http://dx.doi.org/10.4161/onci.28327 PubMed DOI PMC

Yeh S, Karne NK, Kerkar SP, Heller CK, Palmer DC, Johnson LA, Li Z, Bishop RJ, Wong WT, Sherry RM et al.. Ocular and systemic autoimmunity after successful tumor-infiltrating lymphocyte immunotherapy for recurrent, metastatic melanoma. Ophthalmology 2009; 116:981-9.e1; PMID:19410956; http://dx.doi.org/10.1016/j.ophtha.2008.12.004 PubMed DOI PMC

Morgan RA, Chinnasamy N, Abate-Daga D, Gros A, Robbins PF, Zheng Z, Dudley ME, Feldman SA, Yang JC, Sherry RM et al.. Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy. J Immunother 2013; 36:133-51; PMID:23377668; http://dx.doi.org/10.1097/CJI.0b013e3182829903 PubMed DOI PMC

Xu XJ, Tang YM. Cytokine release syndrome in cancer immunotherapy with chimeric antigen receptor engineered T cells. Cancer Lett 2014; 343:172-8; PMID:24141191; http://dx.doi.org/10.1016/j.canlet.2013.10.004 PubMed DOI

Morgan RA. Risky business: target choice in adoptive cell therapy. Blood 2013; 122:3392-4; PMID:24235126; http://dx.doi.org/10.1182/blood-2013-09-527622 PubMed DOI PMC

Ruella M, Kalos M. Adoptive immunotherapy for cancer. Immunol Rev 2014; 257:14-38; PMID:24329787; http://dx.doi.org/10.1111/imr.12136 PubMed DOI

Maude SL, Barrett D, Teachey DT, Grupp SA. Managing cytokine release syndrome associated with novel T cell-engaging therapies. Cancer J 2014; 20:119-22; PMID:24667956; http://dx.doi.org/10.1097/PPO.0000000000000035 PubMed DOI PMC

Teachey DT, Rheingold SR, Maude SL, Zugmaier G, Barrett DM, Seif AE, Nichols KE, Suppa EK, Kalos M, Berg RA et al.. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood 2013; 121:5154-7; PMID:23678006; http://dx.doi.org/10.1182/blood-2013-02-485623 PubMed DOI PMC

Pegram HJ, Jackson JT, Smyth MJ, Kershaw MH, Darcy PK. Adoptive transfer of gene-modified primary NK cells can specifically inhibit tumor progression in vivo. J Immunol 2008; 181:3449-55; PMID:18714017; http://dx.doi.org/10.4049/jimmunol.181.5.3449 PubMed DOI

Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, Posati S, Rogaia D, Frassoni F, Aversa F et al.. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 2002; 295:2097-100; PMID:11896281; http://dx.doi.org/10.1126/science.1068440 PubMed DOI

Velardi A, Ruggeri L, Mancusi A, Aversa F, Christiansen FT. Natural killer cell allorecognition of missing self in allogeneic hematopoietic transplantation: a tool for immunotherapy of leukemia. Curr Opin Immunol 2009; 21:525-30; PMID:19717293; http://dx.doi.org/10.1016/j.coi.2009.07.015 PubMed DOI

Ohira M, Ohdan H, Mitsuta H, Ishiyama K, Tanaka Y, Igarashi Y, Asahara T. Adoptive transfer of TRAIL-expressing natural killer cells prevents recurrence of hepatocellular carcinoma after partial hepatectomy. Transplantation 2006; 82:1712-9; PMID:17198265; http://dx.doi.org/10.1097/01.tp.0000250935.41034.2d PubMed DOI

Okada K, Nannmark U, Vujanovic NL, Watkins S, Basse P, Herberman RB, Whiteside TL. Elimination of established liver metastases by human interleukin 2-activated natural killer cells after locoregional or systemic adoptive transfer. Cancer Res 1996; 56:1599-608; PMID:8603408 PubMed

Besser MJ, Shoham T, Harari-Steinberg O, Zabari N, Ortenberg R, Yakirevitch A, Nagler A, Loewenthal R, Schachter J, Markel G. Development of allogeneic NK cell adoptive transfer therapy in metastatic melanoma patients: in vitro preclinical optimization studies. PLoS One 2013; 8:e57922; PMID:23483943; http://dx.doi.org/10.1371/journal.pone.0057922 PubMed DOI PMC

Terme M, Fridman WH, Tartour E. NK cells from pleural effusions are potent antitumor effector cells. Eur J Immunol 2013; 43:331-4; PMID:23322344; http://dx.doi.org/10.1002/eji.201243264 PubMed DOI

Lister J, Rybka WB, Donnenberg AD, deMagalhaes-Silverman M, Pincus SM, Bloom EJ, Elder EM, Ball ED, Whiteside TL. Autologous peripheral blood stem cell transplantation and adoptive immunotherapy with activated natural killer cells in the immediate posttransplant period. Clin Cancer Res 1995; 1:607-14; PMID:9816022 PubMed

Parkhurst MR, Riley JP, Dudley ME, Rosenberg SA. Adoptive transfer of autologous natural killer cells leads to high levels of circulating natural killer cells but does not mediate tumor regression. Clin Cancer Res 2011; 17:6287-97; PMID:21844012; http://dx.doi.org/10.1158/1078-0432.CCR-11-1347 PubMed DOI PMC

Iliopoulou EG, Kountourakis P, Karamouzis MV, Doufexis D, Ardavanis A, Baxevanis CN, Rigatos G, Papamichail M, Perez SA. A phase I trial of adoptive transfer of allogeneic natural killer cells in patients with advanced non-small cell lung cancer. Cancer Immunol Immunother 2010; 59:1781-9; PMID:20703455; http://dx.doi.org/10.1007/s00262-010-0904-3 PubMed DOI PMC

Badoual C, Bastier PL, Roussel H, Mandavit M, Tartour E. An allogeneic NK cell line engineered to express chimeric antigen receptors: a novel strategy of cellular immunotherapy against cancer. Oncoimmunology 2013; 2:e27156; PMID:24753987; http://dx.doi.org/10.4161/onci.27156 PubMed DOI PMC

Boissel L, Betancur-Boissel M, Lu W, Krause DS, Van Etten RA, Wels WS, Klingemann H. Retargeting NK-92 cells by means of CD19- and CD20-specific chimeric antigen receptors compares favorably with antibody-dependent cellular cytotoxicity. Oncoimmunology 2013; 2:e26527; PMID:24404423; http://dx.doi.org/10.4161/onci.26527 PubMed DOI PMC

Altvater B, Landmeier S, Pscherer S, Temme J, Schweer K, Kailayangiri S, Campana D, Juergens H, Pule M, Rossig C. 2B4 (CD244) signaling by recombinant antigen-specific chimeric receptors costimulates natural killer cell activation to leukemia and neuroblastoma cells. Clin Cancer Res 2009; 15:4857-66; PMID:19638467; http://dx.doi.org/10.1158/1078-0432.CCR-08-2810 PubMed DOI PMC

Boissel L, Betancur M, Wels WS, Tuncer H, Klingemann H. Transfection with mRNA for CD19 specific chimeric antigen receptor restores NK cell mediated killing of CLL cells. Leuk Res 2009; 33:1255-9; PMID:19147228; http://dx.doi.org/10.1016/j.leukres.2008.11.024 PubMed DOI PMC

Vacca P, Martini S, Mingari MC, Moretta L. NK cells from malignant pleural effusions are potent antitumor effectors: A clue for adoptive immunotherapy? Oncoimmunology 2013; 2:e23638; PMID:23734317; http://dx.doi.org/10.4161/onci.23638 PubMed DOI PMC

Vacchelli E, Galluzzi L, Eggermont A, Galon J, Tartour E, Zitvogel L, Kroemer G. Trial Watch: immunostimulatory cytokines. Oncoimmunology 2012; 1:493-506; PMID:22754768; http://dx.doi.org/10.4161/onci.20459 PubMed DOI PMC

Vacchelli E, Martins I, Eggermont A, Fridman WH, Galon J, Sautes-Fridman C, Tartour E, Zitvogel L, Kroemer G, Galluzzi L. Trial watch: peptide vaccines in cancer therapy. Oncoimmunology 2012; 1:1557-76; PMID:23264902; http://dx.doi.org/10.4161/onci.22428 PubMed DOI PMC

Aranda F, Vacchelli E, Obrist F, Eggermont A, Galon J, Herve Fridman W, Cremer I, Tartour E, Zitvogel L, Kroemer G et al.. Trial Watch: adoptive cell transfer for anticancer immunotherapy. Oncoimmunology 2014; 3:e28344; PMID:25050207; http://dx.doi.org/10.4161/onci.28344 PubMed DOI PMC

Park JH, Riviere I, Wang X, Bartido S, Sadelain M, Brentjens RJ. Phase I trial of autologous CD19-targeted CAR-modified t cells as consolidation after purine analog-based first-line therapy in patients with previously untreated CLL. ASCO Meeting Abstracts 2014; 32:7020

Wang Y, Zhang WY, Han QW, Liu Y, Dai HR, Guo YL, Bo J, Fan H, Zhang Y, Zhang YJ et al.. Effective response and delayed toxicities of refractory advanced diffuse large B-cell lymphoma treated by CD20-directed chimeric antigen receptor-modified T cells. Clin Immunol 2014; 155:160-75; PMID:25444722; http://dx.doi.org/10.1016/j.clim.2014.10.002 PubMed DOI

Chodon T, Comin-Anduix B, Chmielowski B, Koya RC, Wu Z, Auerbach M, Ng C, Avramis E, Seja E, Villanueva A et al.. Adoptive transfer of MART-1 T-cell receptor transgenic lymphocytes and dendritic cell vaccination in patients with metastatic melanoma. Clin Cancer Res 2014; 20:2457-65; PMID:24634374; http://dx.doi.org/10.1158/1078-0432.CCR-13-3017 PubMed DOI PMC

Robbins PF, Kassim SH, Tran TL, Crystal JS, Morgan RA, Feldman SA, Yang JC, Dudley ME, Wunderlich JR, Sherry RM et al.. A pilot trial using lymphocytes genetically engineered with an NY-ESO-1-Reactive T-cell receptor: long-term follow-up and correlates with response. Clin Cancer Res 2015; 21:1019-27; PMID:25538264; http://dx.doi.org/10.1158/1078-0432.CCR-14-2708 PubMed DOI PMC

Johnson LA, Scholler J, Ohkuri T, Kosaka A, Patel PR, McGettigan SE, Nace AK, Dentchev T, Thekkat P, Loew A et al.. Rational development and characterization of humanized anti-EGFR variant III chimeric antigen receptor T cells for glioblastoma. Sci Transl Med 2015; 7:275ra22; PMID:25696001; http://dx.doi.org/10.1126/scitranslmed.aaa4963 PubMed DOI PMC

Adusumilli PS, Cherkassky L, Villena-Vargas J, Colovos C, Servais E, Plotkin J, Jones DR, Sadelain M. Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity. Sci Transl Med 2014; 6:261ra151; PMID:25378643; http://dx.doi.org/10.1126/scitranslmed.3010162 PubMed DOI PMC

Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, Fry TJ, Orentas R, Sabatino M, Shah NN et al.. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet 2015; 385:517-28; PMID:25319501; http://dx.doi.org/10.1016/S0140-6736(14)61403-3 PubMed DOI PMC

Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF et al.. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med 2014; 371:1507-17; PMID:25317870; http://dx.doi.org/10.1056/NEJMoa1407222 PubMed DOI PMC

Poschke I, Lovgren T, Adamson L, Nystrom M, Andersson E, Hansson J, Tell R, Masucci GV, Kiessling R. A phase I clinical trial combining dendritic cell vaccination with adoptive T cell transfer in patients with stage IV melanoma. Cancer Immunol Immunother 2014; 63:1061-71; PMID:24993563; http://dx.doi.org/10.1007/s00262-014-1575-2 PubMed DOI PMC

Romano E, Michielin O, Voelter V, Laurent J, Bichat H, Stravodimou A, Romero P, Speiser DE, Triebel F, Leyvraz S et al.. MART-1 peptide vaccination plus IMP321 (LAG-3Ig fusion protein) in patients receiving autologous PBMCs after lymphodepletion: results of a Phase I trial. J Transl Med 2014; 12:97; PMID:24726012; http://dx.doi.org/10.1186/1479-5876-12-97 PubMed DOI PMC

Chandran SS, Paria BC, Srivastava AK, Rothermel LD, Stephens DJ, Dudley ME, Somerville R, Wunderlich JR, Sherry RM, Yang JC. Persistence of CTL clones targeting melanocyte differentiation antigens was insufficient to mediate significant melanoma regression in humans. Clin Cancer Res 2015; 21:534-43; PMID:25424856; http://dx.doi.org/10.1158/1078-0432.CCR-14-2208 PubMed DOI PMC

Rapoport AP, Aqui NA, Stadtmauer EA, Vogl DT, Xu YY, Kalos M, Cai L, Fang HB, Weiss BM, Badros A et al.. Combination immunotherapy after ASCT for multiple myeloma using MAGE-A3/Poly-ICLC immunizations followed by adoptive transfer of vaccine-primed and costimulated autologous T cells. Clin Cancer Res 2014; 20:1355-65; PMID:24520093; http://dx.doi.org/10.1158/1078-0432.CCR-13-2817 PubMed DOI PMC

Tran E, Turcotte S, Gros A, Robbins PF, Lu YC, Dudley ME, Wunderlich JR, Somerville RP, Hogan K, Hinrichs CS et al.. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science 2014; 344:641-5; PMID:24812403; http://dx.doi.org/10.1126/science.1251102 PubMed DOI PMC

Tseng J, Citrin DE, Waldman M, White DE, Rosenberg SA, Yang JC. Thrombotic microangiopathy in metastatic melanoma patients treated with adoptive cell therapy and total body irradiation. Cancer 2014; 120:1426-32; PMID:24474396; http://dx.doi.org/10.1002/cncr.28547 PubMed DOI PMC

Schuessler A, Smith C, Beagley L, Boyle GM, Rehan S, Matthews K, Jones L, Crough T, Dasari V, Klein K et al.. Autologous T-cell therapy for cytomegalovirus as a consolidative treatment for recurrent glioblastoma. Cancer Res 2014; 74:3466-76; PMID:24795429; http://dx.doi.org/10.1158/0008-5472.CAN-14-0296 PubMed DOI

Gallot G, Vollant S, Saiagh S, Clemenceau B, Vivien R, Cerato E, Bignon JD, Ferrand C, Jaccard A, Vigouroux S et al.. T-cell therapy using a bank of EBV-specific cytotoxic T cells: lessons from a phase I/II feasibility and safety study. J Immunother 2014; 37:170-9; PMID:24598452; http://dx.doi.org/10.1097/CJI.0000000000000031 PubMed DOI

Tell R, Mattson J, Adamson L, Poschke I, Engstrom M, Lovgren T, Hansson J, Masucci GV, Lundqvist A, Kiessling R. A phase I study of adoptive T-cell therapy with or without dendritic cell vaccination in patients with metastatic melanoma. ASCO Meet Abstr 2014; 32:TPS3118

Disis ML, Coveler AL, Higgins D, D'Amico LA, Morishima C, Waisman JR, Reichow J, Childs J, Dang Y, Salazar LG et al.. Phase I/II study of adoptive T-cell therapy following in vivo priming with a HER2/neu vaccine in patients with advanced-stage HER2+ breast cancer. ASCO Meet Abstr 2014; 32:615

Glitza IC, Bernatchez C, Bassett RL, Vaughn C, Velasquez P, Diab A, Amaria RN, Yee C, Woodman SE, Patel SP et al.. Treatment with tumor-infiltrating lymphocytes (TIL) in metastatic melanoma and clinical benefit regardless of site of origin, mutation status, or prior checkpoint blockade. ASCO Meeting Abstr 2014; 32:9079

Hinrichs CS, Stevanovic S, Draper L, Somerville R, Wunderlich J, Restifo NP, Sherry R, Giao PQ, Kammula US, Yang, JC et al.. HPV-targeted tumor-infiltrating lymphocytes for cervical cancer. ASCO Meet Abstr 2014; 32:LBA3008

Wang ZX, Cao JX, Wang M, Li D, Cui YX, Zhang XY, Liu JL, Li JL. Adoptive cellular immunotherapy for the treatment of patients with breast cancer: a meta-analysis. Cytotherapy 2014; 16:934-45; PMID:24794183; http://dx.doi.org/10.1016/j.jcyt.2014.02.011 PubMed DOI

Chung MJ, Park JY, Bang S, Park SW, Song SY. Phase II clinical trial of ex vivo-expanded cytokine-induced killer cells therapy in advanced pancreatic cancer. Cancer Immunol Immunother 2014; 63:939-46; PMID:24916038; http://dx.doi.org/10.1007/s00262-014-1566-3 PubMed DOI PMC

Shi SB, Tang XY, Tian J, Chang CX, Li P, Qi JL. Efficacy of erlotinib plus dendritic cells and cytokine-induced killer cells in maintenance therapy of advanced non-small cell lung cancer. J Immunother 2014; 37:250-5; PMID:24714359; http://dx.doi.org/10.1097/CJI.0000000000000015 PubMed DOI

Killig M, Friedrichs B, Meisig J, Gentilini C, Bluthgen N, Loddenkemper C, Labopin M, Basara N, Pfrepper C, Niederwieser DW et al.. Tracking in vivo dynamics of NK cells transferred in patients undergoing stem cell transplantation. Eur J Immunol 2014; 44:2822-34; PMID:24895051; http://dx.doi.org/10.1002/eji.201444586 PubMed DOI

Kimura H, Matsui Y, Ishikawa A, Nakajima T, Yoshino M, Sakairi Y. Randomized controlled phase III trial of adjuvant chemo-immunotherapy with activated killer T cells and dendritic cells in patients with resected primary lung cancer. Cancer Immunol Immunother 2015; 64:51-9; PMID:25262164; http://dx.doi.org/10.1007/s00262-014-1613-0 PubMed DOI PMC

Crompton JG, Sukumar M, Roychoudhuri R, Clever D, Gros A, Eil RL, Tran E, Hanada K, Yu Z, Palmer DC et al.. Akt inhibition enhances expansion of potent tumor-specific lymphocytes with memory cell characteristics. Cancer Res 2015; 75:296-305; PMID:25432172; http://dx.doi.org/10.1158/0008-5472.CAN-14-2277 PubMed DOI PMC

Geng D, Kaczanowska S, Tsai A, Younger K, Ochoa A, Rapoport AP, Ostrand-Rosenberg S, Davila E. TLR5 ligand-secreting T cells reshape the tumor microenvironment and enhance antitumor activity. Cancer Res 2015; 75:1959-61; PMID:25795705; http://dx.doi.org/10.1158/0008-5472.CAN-14-2467 PubMed DOI PMC

Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Immunogenic cell death in cancer therapy. Annu Rev Immunol 2013; 31:51-72; PMID:23157435; http://dx.doi.org/10.1146/annurev-immunol-032712-100008 PubMed DOI

Gardai SJ, McPhillips KA, Frasch SC, Janssen WJ, Starefeldt A, Murphy-Ullrich JE, Bratton DL, Oldenborg PA, Michalak M, Henson PM. Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte. Cell 2005; 123:321-34; PMID:16239148; http://dx.doi.org/10.1016/j.cell.2005.08.032 PubMed DOI

Kepp O, Galluzzi L, Martins I, Schlemmer F, Adjemian S, Michaud M, Sukkurwala AQ, Menger L, Zitvogel L, Kroemer G. Molecular determinants of immunogenic cell death elicited by anticancer chemotherapy. Cancer Metastasis Rev 2011; 30:61-9; PMID:21249425; http://dx.doi.org/10.1007/s10555-011-9273-4 PubMed DOI

Soto-Pantoja DR, Terabe M, Ghosh A, Ridnour LA, DeGraff WG, Wink DA, Berzofsky JA, Roberts DD. CD47 in the tumor microenvironment limits cooperation between antitumor T-cell immunity and radiotherapy. Cancer Res 2014; 74:6771-83; PMID:25297630; http://dx.doi.org/10.1158/0008-5472.CAN-14-0037-T PubMed DOI PMC

Galluzzi L, Kepp O, Kroemer G. Immunogenic cell death in radiation therapy. Oncoimmunology 2013; 2:e26536; PMID:24404424; http://dx.doi.org/10.4161/onci.26536 PubMed DOI PMC

Vacchelli E, Vitale I, Tartour E, Eggermont A, Sautes-Fridman C, Galon J, Zitvogel L, Kroemer G, Galluzzi L. Trial Watch: anticancer radioimmunotherapy. Oncoimmunology 2013; 2:e25595; PMID:24319634; http://dx.doi.org/10.4161/onci.25595 PubMed DOI PMC

Huang YH, Zhu C, Kondo Y, Anderson AC, Gandhi A, Russell A, Dougan SK, Petersen BS, Melum E, Pertel T et al.. CEACAM1 regulates TIM-3-mediated tolerance and exhaustion. Nature 2015; 517:386-90; PMID:25363763; http://dx.doi.org/10.1038/nature13848 PubMed DOI PMC

Lin R, Chen L, Chen G, Hu C, Jiang S, Sevilla J, Wan Y, Sampson JH, Zhu B, Li QJ. Targeting miR-23a in CD8+ cytotoxic T lymphocytes prevents tumor-dependent immunosuppression. J Clin Invest 2014; 124:5352-67; PMID:25347474; http://dx.doi.org/10.1172/JCI76561 PubMed DOI PMC

Caruana I, Savoldo B, Hoyos V, Weber G, Liu H, Kim ES, Ittmann MM, Marchetti D, Dotti G. Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes. Nat Med 2015; 21:524-9; PMID:25849134; http://dx.doi.org/10.1038/nm.3833 PubMed DOI PMC

Motz GT, Santoro SP, Wang LP, Garrabrant T, Lastra RR, Hagemann IS, Lal P, Feldman MD, Benencia F, Coukos G. Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors. Nat Med 2014; 20:607-15; PMID:24793239; http://dx.doi.org/10.1038/nm.3541 PubMed DOI PMC

Galluzzi L, Bravo-San Pedro JM, Vitale I, Aaronson SA, Abrams JM, Adam D, Alnemri ES, Altucci L, Andrews D, Annicchiarico-Petruzzelli M et al.. Essential versus accessory aspects of cell death: recommendations of the NCCD 2015. Cell Death Differ 2015; 22:58-73; PMID:25236395; http://dx.doi.org/10.1038/cdd.2014.137 PubMed DOI PMC

Galluzzi L, Bravo-San Pedro JM, Kroemer G. Organelle-specific initiation of cell death. Nat Cell Biol 2014; 16:728-36; PMID:25082195; http://dx.doi.org/10.1038/ncb3005 PubMed DOI

Kudo K, Imai C, Lorenzini P, Kamiya T, Kono K, Davidoff AM, Chng WJ, Campana D. T lymphocytes expressing a CD16 signaling receptor exert antibody-dependent cancer cell killing. Cancer Res 2014; 74:93-103; PMID:24197131; http://dx.doi.org/10.1158/0008-5472.CAN-13-1365 PubMed DOI

Galluzzi L, Vacchelli E, Fridman WH, Galon J, Sautes-Fridman C, Tartour E, Zucman-Rossi J, Zitvogel L, Kroemer G. Trial Watch: Monoclonal antibodies in cancer therapy. Oncoimmunology 2012; 1:28-37; PMID:22720209; http://dx.doi.org/10.4161/onci.1.1.17938 PubMed DOI PMC

Vacchelli E, Eggermont A, Galon J, Sautes-Fridman C, Zitvogel L, Kroemer G, Galluzzi L. Trial watch: Monoclonal antibodies in cancer therapy. Oncoimmunology 2013; 2:e22789; PMID:24605265; http://dx.doi.org/10.4161/onci.27048 PubMed DOI PMC

Okosieme OE, Evans C, Moss L, Parkes AB, Premawardhana LD, Lazarus JH. Thyroglobulin antibodies in serum of patients with differentiated thyroid cancer: relationship between epitope specificities and thyroglobulin recovery. Clin Chem 2005; 51:729-34; PMID:15695326; http://dx.doi.org/10.1373/clinchem.2004.044511 PubMed DOI

Morishita M, Uchimaru K, Sato K, Ohtsuru A, Yamashita S, Kanematsu T, Yamashita N. Thyroglobulin-pulsed human monocyte-derived dendritic cells induce CD4+ T cell activation. Int J Mol Med 2004; 13:33-9; PMID:14654967; http://dx.doi.org/10.3892/ijmm.13.1.33 PubMed DOI

Yu AL, Gilman AL, Ozkaynak MF, London WB, Kreissman SG, Chen HX, Smith M, Anderson B, Villablanca JG, Matthay KK et al.. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med 2010; 363:1324-34; PMID:20879881; http://dx.doi.org/10.1056/NEJMoa0911123 PubMed DOI PMC

Louis CU, Savoldo B, Dotti G, Pule M, Yvon E, Myers GD, Rossig C, Russell HV, Diouf O, Liu E et al.. Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma. Blood 2011; 118:6050-6; PMID:21984804; http://dx.doi.org/10.1182/blood-2011-05-354449 PubMed DOI PMC

Cheung NK, Guo H, Hu J, Tassev DV, Cheung IY. Humanizing murine IgG3 anti-GD2 antibody m3F8 substantially improves antibody-dependent cell-mediated cytotoxicity while retaining targeting in vivo. Oncoimmunology 2012; 1:477-86; PMID:22754766; http://dx.doi.org/10.4161/onci.19864 PubMed DOI PMC

Vincent M, Quemener A, Jacques Y. Antitumor activity of an immunocytokine composed of an anti-GD2 antibody and the IL-15 superagonist RLI. Oncoimmunology 2013; 2:e26441; PMID:24349876; http://dx.doi.org/10.4161/onci.26441 PubMed DOI PMC

Choi BK, Lee SC, Lee MJ, Kim YH, Kim YW, Ryu KW, Lee JH, Shin SM, Lee SH, Suzuki S et al.. 4-1BB-based isolation and expansion of CD8+ T cells specific for self-tumor and non-self-tumor antigens for adoptive T-cell therapy. J Immunother 2014; 37:225-36; PMID:24714356; http://dx.doi.org/10.1097/CJI.0000000000000027 PubMed DOI

Kershaw MH, Westwood JA, Slaney CY, Darcy PK. Clinical application of genetically modified T cells in cancer therapy. Clin Transl Immunology 2014; 3:e16; PMID:25505964; http://dx.doi.org/10.1038/cti.2014.7 PubMed DOI PMC

Trial Watch: Immunotherapy plus radiation therapy for oncological indications