Prospects for chimeric antigen receptor (CAR) γδ T cells: A potential game changer for adoptive T cell cancer immunotherapy

Cancer Letters

Volumn 380, Issue 2, 2016, Pages 413-423

  Mirzaei, Hamid Reza ^a,b   Mirzaei, Hamed ^c   Yun Lee, Sang ^b   Hadjati, Jamshid ^a   Till, Brian G ^b  

^a TEHRAN UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^b USA   (United States)

^c MASHHAD UNIVERSITY OF MEDICAL SCIENCES   (Iran)

Author keywords

Cancer therapy; Chimeric antigen receptor; T cells

Indexed keywords

CHIMERIC ANTIGEN RECEPTOR; HYBRID PROTEIN; LYMPHOCYTE ANTIGEN RECEPTOR;

ACUTE LYMPHOBLASTIC LEUKEMIA; ACUTE MYELOBLASTIC LEUKEMIA; ADOPTIVE TRANSFER; ALLOIMMUNITY; ANTIGEN PRESENTATION; CANCER IMMUNOTHERAPY; CELL MANIPULATION; CELL MATURATION; CELL THERAPY; CYTOKINE PRODUCTION; GAMMA DELTA T LYMPHOCYTE; GENETIC ENGINEERING; HUMAN; IMMUNE RESPONSE; KIDNEY CARCINOMA; MUCOSAL CANCER; MULTIPLE MYELOMA; NONHODGKIN LYMPHOMA; NONHUMAN; PLASMA CELL LEUKEMIA; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; SHORT SURVEY; TISSUE DISTRIBUTION; TREATMENT PLANNING; ADOPTIVE IMMUNOTHERAPY; ANIMAL; BIOSYNTHESIS; GENE THERAPY; GENETICS; IMMUNOLOGY; METABOLISM; NEOPLASMS; PATHOLOGY; PHENOTYPE; PROCEDURES; T LYMPHOCYTE; T LYMPHOCYTE RECEPTOR GENE; TRANSPLANTATION; TUMOR ASSOCIATED LEUKOCYTE; TUMOR MICROENVIRONMENT;

ANIMALS; GENES, T-CELL RECEPTOR DELTA; GENES, T-CELL RECEPTOR GAMMA; GENETIC THERAPY; HUMANS; IMMUNOTHERAPY, ADOPTIVE; LYMPHOCYTES, TUMOR-INFILTRATING; NEOPLASMS; PHENOTYPE; RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA; RECOMBINANT FUSION PROTEINS; T-LYMPHOCYTES; TUMOR MICROENVIRONMENT;

EID: 84984918851     PISSN: 03043835     EISSN: 18727980     Source Type: Journal    
DOI: 10.1016/j.canlet.2016.07.001     Document Type: Review

References (164)

1. [1] Yee, C., Gilbert, M.J., Riddell, S.R., Brichard, V.G., Fefer, A., Thompson, J.A., et al. Isolation of tyrosinase-specific CD8+ and CD4+ T cell clones from the peripheral blood of melanoma patients following in vitro stimulation with recombinant vaccinia virus. J. Immunol 157:9 (1996), 4079–4086.
2. [2] Hughes, M.S., Yu, Y.Y., Dudley, M.E., Zheng, Z., Robbins, P.F., Li, Y., et al. Transfer of a TCR gene derived from a patient with a marked antitumor response conveys highly active T-cell effector functions. Hum. Gene Ther 16:4 (2005), 457–472.
3. [3] Beatty, G.L., Haas, A.R., Maus, M.V., Torigian, D.A., Soulen, M.C., Plesa, G., et al. Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce antitumor activity in solid malignancies. Cancer Immunol. Res 2:2 (2014), 112–120.
4. [4] Barrett, D.M., Grupp, S.A., June, C.H., Chimeric antigen receptor–and TCR-modified T cells enter main street and wall street. J. Immunol 195:3 (2015), 755–761.
5. [5] Louis, C.U., Savoldo, B., Dotti, G., Pule, M., Yvon, E., Myers, G.D., et al. Antitumor activity and long-term fate of chimeric antigen receptor–positive T cells in patients with neuroblastoma. Blood 118:23 (2011), 6050–6056.
6. [6] Pule, M.A., Savoldo, B., Myers, G.D., Rossig, C., Russell, H.V., Dotti, G., et al. Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma. Nat. Med 14:11 (2008), 1264–1270.
7. [7] Rosenberg, S.A., Packard, B.S., Aebersold, P.M., Solomon, D., Topalian, S.L., Toy, S.T., et al. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. NEJM 319:25 (1988), 1676–1680.
8. [8] Rosenberg, S.A., Yang, J.C., Sherry, R.M., Kammula, U.S., Hughes, M.S., Phan, G.Q., et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin. Cancer Res 17:13 (2011), 4550–4557.
9. [9] Stevanović, S., Draper, L.M., Langhan, M.M., Campbell, T.E., Kwong, M.L., Wunderlich, J.R., et al. Complete regression of metastatic cervical cancer after treatment with human papillomavirus–targeted tumor-infiltrating T cells. J. Clin. Oncol, 2014(58), 2015, 9093.
10. [10] Singh, H., Huls, H., Kebriaei, P., Cooper, L.J., A new approach to gene therapy using Sleeping Beauty to genetically modify clinical-grade T cells to target CD19. Immunol. Rev 257:1 (2014), 181–190.
11. [11] Kochenderfer, J.N., Wilson, W.H., Janik, J.E., Dudley, M.E., Stetler-Stevenson, M., Feldman, S.A., 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 116:20 (2010), 4099–4102.
12. [12] Brentjens, R.J., Davila, M.L., Riviere, I., Park, J., Wang, X., Cowell, L.G., et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci. Transl. Med, 5(177), 2013 177ra38.
13. [13] Kochenderfer, J.N., Dudley, M.E., Kassim, S.H., Somerville, R.P., Carpenter, R.O., Stetler-Stevenson, M., et al. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J. Clin. Oncol 33:6 (2015), 540–549.
14. [14] Lamers, C.H., Sleijfer, S., van Steenbergen, S., van Elzakker, P., van Krimpen, B., Groot, C., et al. Treatment of metastatic renal cell carcinoma with CAIX CAR-engineered T cells: clinical evaluation and management of on-target toxicity. Mol. Ther 21:4 (2013), 904–912.
15. [15] Kershaw, M.H., Westwood, J.A., Parker, L.L., Wang, G., Eshhar, Z., Mavroukakis, S.A., et al. A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin. Cancer Res 12:20 (2006), 6106–6115.
16. [16] Deniger, D.C., Switzer, K., Mi, T., Maiti, S., Hurton, L., Singh, H., et al. Bispecific T-cells expressing polyclonal repertoire of endogenous γδ T-cell receptors and introduced CD19-specific chimeric antigen receptor. Mol. Ther 21:3 (2013), 638–647.
17. [17] Mocellin, S., Wang, E., Marincola, F.M., Cytokines and immune response in the tumor microenvironment. J. Immunother 24:5 (2001), 392–407.
18. [18] Mantovani, A., Romero, P., Palucka, A.K., Marincola, F.M., Tumour immunity: effector response to tumour and role of the microenvironment. Lancet 371:9614 (2008), 771–783.
19. [19] Munn, D.H., Bronte, V., Immune suppressive mechanisms in the tumor microenvironment. Curr. Opin. Immunol 39 (2016), 1–6.
20. [20] Medler, T.R., Cotechini, T., Coussens, L.M., Immune response to cancer therapy: mounting an effective antitumor response and mechanisms of resistance. Trends Cancer 1:1 (2015), 66–75.
21. [21] Asarnow, D.M., Goodman, T., LeFrancois, L., Allison, J.P., Distinct antigen receptor repertoires of two classes of murine epithelium-associated T cells. 1989.
22. [22] Chen, Y., Chou, K., Fuchs, E., Havran, W.L., Boismenu, R., Protection of the intestinal mucosa by intraepithelial γδ T cells. Proc. Natl. Acad. Sci. U.S.A. 99:22 (2002), 14338–14343.
23. [23] Boismenu, R., Havran, W.L., γδ T cells in host defense and epithelial cell biology. Clin. Immunol. Immunopathol 86:2 (1998), 121–133.
24. [24] Groh, V., Steinle, A., Bauer, S., Spies, T., Recognition of stress-induced MHC molecules by intestinal epithelial γδ T cells. Science 279:5357 (1998), 1737–1740.
25. [25] Groh, V., Rhinehart, R., Secrist, H., Bauer, S., Grabstein, K.H., Spies, T., Broad tumor-associated expression and recognition by tumor-derived γδ T cells of MICA and MICB. Proc. Natl. Acad. Sci. U.S.A. 96:12 (1999), 6879–6884.
26. [26] Taghon, T., Yui, M.A., Pant, R., Diamond, R.A., Rothenberg, E.V., Developmental and molecular characterization of emerging β-and γδ-selected pre-T cells in the adult mouse thymus. Immunity 24:1 (2006), 53–64.
27. [27] Lefrancois, L., LeCorre, R., Mayo, J., Bluestone, J.A., Goodman, T., Extrathymic selection of TCR γδ+ T cells by class II major histocompatibility complex molecules. Cell 63:2 (1990), 333–340.
28. [28] Cowan, J.E., Jenkinson, W.E., Anderson, G., Thymus medulla fosters generation of natural Treg cells, invariant γδ T cells, and invariant NKT cells: what we learn from intrathymic migration. Eur. J. Immunol 45:3 (2015), 652–660.
29. [29] Carding, S.R., Kyes, S., Jenkinson, E.J., Kingston, R., Bottomly, K., Owen, J.J., et al. Developmentally regulated fetal thymic and extrathymic T-cell receptor gamma delta gene expression. Genes Dev 4:8 (1990), 1304–1315 2227410 Epub 1990/08/01. eng.
30. [30] Heilig, J.S., Tonegawa, S., Diversity of murine gamma genes and expression in fetal and adult T lymphocytes. Nature 322:6082 (1986), 836–840 2943999 Epub 1986/08/03. eng.
31. [31] Ikuta, K., Kina, T., MacNeil, I., Uchida, N., Peault, B., Chien, Y.H., et al. A developmental switch in thymic lymphocyte maturation potential occurs at the level of hematopoietic stem cells. Cell 62:5 (1990), 863–874 1975515 Epub 1990/09/07. eng.
32. [32] McVay, L.D., Carding, S.R., Generation of human gammadelta T-cell repertoires. Crit. Rev. Immunol 19:5–6 (1999), 431–460 10647745 Epub 2000/01/27. eng.
33. [33] Hayday, A.C., γδ cells: a right time and a right place for a conserved third way of protection. Annu. Rev. Immunol 18:1 (2000), 975–1026.
34. [34] Lafaille, J.J., DeCloux, A., Bonneville, M., Takagaki, Y., Tonegawa, S., Junctional sequences of T cell receptor γδ genes: implications for γδ T cell lineages and for a novel intermediate of V-(D)-J joining. Cell 59:5 (1989), 859–870.
35. [35] Itohara, S., Mombaerts, P., Lafaille, J., Iacomini, J., Nelson, A., Clarke, A.R., et al. T cell receptor δ gene mutant mice: independent generation of αβ T cells and programmed rearrangements of γδ TCR genes. Cell 72:3 (1993), 337–348.
36. [36] Adams, E.J., Gu, S., Luoma, A.M., Human gamma delta T cells: evolution and ligand recognition. Cell. Immunol 296:1 (2015), 31–40.
37. [37] Kabelitz, D., Déchanet-Merville, J., Editorial:“Recent advances in gamma/delta T cell biology: new ligands, new functions, and new translational perspectives”. Front. Immunol, 6, 2015.
38. [38] Constant, P., Davodeau, F., Peyrat, M.-A., Poquet, Y., Puzo, G., Bonneville, M., et al. Stimulation of human gamma delta T cells by nonpeptidic mycobacterial ligands. Science 264:5156 (1994), 267–270.
39. [39] Bruder, J., Siewert, K., Obermeier, B., Malotka, J., Scheinert, P., Kellermann, J., et al. Target specificity of an autoreactive pathogenic human γδ-T cell receptor in myositis. J. Biol. Chem 287:25 (2012), 20986–20995.
40. [40] Willcox, C.R., Pitard, V., Netzer, S., Couzi, L., Salim, M., Silberzahn, T., et al. Cytomegalovirus and tumor stress surveillance by binding of a human [gamma][delta] T cell antigen receptor to endothelial protein C receptor. Nat. Immunol 13:9 (2012), 872–879.
41. [41] Bukowski, J.F., Morita, C.T., Brenner, M.B., Human γδ T cells recognize alkylamines derived from microbes, edible plants, and tea: implications for innate immunity. Immunity 11:1 (1999), 57–65.
42. [42] Ali, Z., Shao, L., Halliday, L., Reichenberg, A., Hintz, M., Jomaa, H., et al. Prolonged (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate-driven antimicrobial and cytotoxic responses of pulmonary and systemic Vgamma2Vdelta2 T cells in macaques. J. Immunol 179:12 (2007), 8287–8296 18056373 Pubmed Central PMCID: PMC2865221. Epub 2007/12/07. eng.
43. [43] Bieback, K., Breer, C., Nanan, R., ter Meulen, V., Schneider-Schaulies, S., Expansion of human gamma/delta T cells in vitro is differentially regulated by the measles virus glycoproteins. J. Gen. Virol 84:Pt 5 (2003), 1179–1188 12692283 Epub 2003/04/15. eng.
44. [44] Espinosa, E., Belmant, C., Pont, F., Luciani, B., Poupot, R., Romagné, F., et al. Chemical synthesis and biological activity of bromohydrin pyrophosphate, a potent stimulator of human γδ T cells. J. Biol. Chem 276:21 (2001), 18337–18344.
45. [45] Gober, H.-J., Kistowska, M., Angman, L., Jenö, P., Mori, L., De Libero, G., Human T cell receptor γδ cells recognize endogenous mevalonate metabolites in tumor cells. J. Exp. Med 197:2 (2003), 163–168.
46. [46] Harly, C., Guillaume, Y., Nedellec, S., Peigne, C.M., Monkkonen, H., Monkkonen, J., et al. Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human gammadelta T-cell subset. Blood 120:11 (2012), 2269–2279 22767497 Pubmed Central PMCID: PMC3679641. Epub 2012/07/07. eng.
47. [47] Mookerjee-Basu, J., Vantourout, P., Martinez, L.O., Perret, B., Collet, X., Périgaud, C., et al. F1-adenosine triphosphatase displays properties characteristic of an antigen presentation molecule for Vγ9Vδ2 T cells. J. Immunol 184:12 (2010), 6920–6928.
48. [48] Scotet, E., Martinez, L.O., Grant, E., Barbaras, R., Jeno, P., Guiraud, M., et al. Tumor recognition following Vgamma9Vdelta2 T cell receptor interactions with a surface F1-ATPase-related structure and apolipoprotein A-I. Immunity 22:1 (2005), 71–80 15664160 Epub 2005/01/25. eng.
49. [49] Kong, Y., Cao, W., Xi, X., Ma, C., Cui, L., He, W., The NKG2D ligand ULBP4 binds to TCRγ9/δ2 and induces cytotoxicity to tumor cells through both TCRγδ and NKG2D. Blood 114:2 (2009), 310–317.
50. [50] Bukowski, J.F., Morita, C.T., Tanaka, Y., Bloom, B.R., Brenner, M.B., Band, H., V gamma 2V delta 2 TCR-dependent recognition of non-peptide antigens and Daudi cells analyzed by TCR gene transfer. J. Immunol 154:3 (1995), 998–1006 7529807 Epub 1995/02/01. eng.
51. [51] Kaur, I., de Jong, J., Schell, K., Hank, J., Fisch, P., Sondel, P.M., Human peripheral gamma delta T cells are stimulated by Daudi Burkitt's lymphoma and not by any other Burkitt's lymphoma tested. Cell. Immunol 156:1 (1994), 54–61 8200042 Epub 1994/06/01. eng.
52. [52] Dai, Y., Chen, H., Mo, C., Cui, L., He, W., Ectopically expressed human tumor biomarker MutS homologue 2 is a novel endogenous ligand that is recognized by human gammadelta T cells to induce innate anti-tumor/virus immunity. J. Biol. Chem 287:20 (2012), 16812–16819 22433851 Pubmed Central PMCID: PMC3351303. Epub 2012/03/22. eng.
53. [53] Vincent, M.S., Roessner, K., Sellati, T., Huston, C.D., Sigal, L.H., Behar, S.M., et al. Lyme arthritis synovial γδ T cells respond to Borrelia burgdorferi lipoproteins and lipidated hexapeptides. J. Immunol 161:10 (1998), 5762–5771.
54. [54] Spada, F.M., Grant, E.P., Peters, P.J., Sugita, M., Melián, A., Leslie, D.S., et al. Self-Recognition of Cd1 by γ/δ T Cells Implications for Innate Immunity. J. Exp. Med 191:6 (2000), 937–948.
55. [55] Johnson, R.M., Lancki, D.W., Sperling, A.I., Dick, R.F., Spear, P., Fitch, F., et al. A murine CD4-, CD8-T cell receptor-gamma delta T lymphocyte clone specific for herpes simplex virus glycoprotein I. J. Immunol 148:4 (1992), 983–988.
56. [56] Xu, B., Pizarro, J.C., Holmes, M.A., McBeth, C., Groh, V., Spies, T., et al. Crystal structure of a γδ T-cell receptor specific for the human MHC class I homolog MICA. Proc. Natl. Acad. Sci. U.S.A. 108:6 (2011), 2414–2419.
57. [57] Bai, L., Picard, D., Anderson, B., Chaudhary, V., Luoma, A., Jabri, B., et al. The majority of CD1d-sulfatide-specific T cells in human blood use a semiinvariant Vδ1 TCR. Eur. J. Immunol 42:9 (2012), 2505–2510.
58. [58] Uldrich, A.P., Le Nours, J., Pellicci, D.G., Gherardin, N.A., McPherson, K.G., Lim, R.T., et al. CD1d-lipid antigen recognition by the [gamma][delta] TCR. Nat. Immunol 14:11 (2013), 1137–1145.
59. [59] Zeng, X., Wei, Y.-L., Huang, J., Newell, E.W., Yu, H., Kidd, B.A., et al. γδ T cells recognize a microbial encoded B cell antigen to initiate a rapid antigen-specific interleukin-17 response. Immunity 37:3 (2012), 524–534.
60. [60] Itohara, S., Farr, A.G., Lafaille, J.J., Bonneville, M., Takagaki, Y., Haas, W., et al. Homing of a gamma delta thymocyte subset with homogeneous T-cell receptors to mucosal epithelia. Nature 343:6260 (1990), 754–757 2154700 Epub 1990/02/22. eng.
61. [61] Kapp, J.A., Kapp, L.M., McKenna, K.C., Lake, J.P., Gammadelta T-cell clones from intestinal intraepithelial lymphocytes inhibit development of CTL responses ex vivo. Immunology 111:2 (2004), 155–164 15027900 Pubmed Central PMCID: PMC1782403. Epub 2004/03/19. eng.
62. [62] Groh, V., Steinle, A., Bauer, S., Spies, T., Recognition of stress-induced MHC molecules by intestinal epithelial gammadelta T cells. Science 279:5357 (1998), 1737–1740 9497295 Epub 1998/03/28. eng.
63. [63] Kabelitz, D., Glatzel, A., Wesch, D., Antigen recognition by human gammadelta T lymphocytes. Int. Arch. Allergy Immunol 122:1 (2000), 1–7 10859464 Epub 2000/06/22. eng.
64. [64] Brandes, M., Willimann, K., Moser, B., Professional antigen-presentation function by human γδ T cells. Science 309:5732 (2005), 264–268.
65. [65] Moser, B., Eberl, M., gammadelta T-APCs: a novel tool for immunotherapy?. Cell. Mol. Life Sci 68:14 (2011), 2443–2452 21573785 Epub 2011/05/17. eng.
66. [66] Li, H., Pauza, C.D., Rapamycin increases the yield and effector function of human gammadelta T cells stimulated in vitro. Cancer Immunol. Immunother 60:3 (2011), 361–370 21107834 Pubmed Central PMCID: PMC3077899. Epub 2010/11/26. eng.
67. [67] Mangan, B.A., Dunne, M.R., O'Reilly, V.P., Dunne, P.J., Exley, M.A., O'Shea, D., et al. Cutting edge: CD1d restriction and Th1/Th2/Th17 cytokine secretion by human Vdelta3 T cells. J. Immunol 191:1 (2013), 30–34 23740951 Pubmed Central PMCID: PMC3721026. Epub 2013/06/07. eng.
68. [68] Matsue, H., Cruz, P.D., Bergstresser, P.R., Takashima, A., Profiles of cytokine mRNA expressed by dendritic epidermal T cells in mice. J. Invest. Dermatol 101:4 (1993), 537–542.
69. [69] Boismenu, R., Feng, L., Xia, Y.Y., Chang, J., Havran, W.L., Chemokine expression by intraepithelial gamma delta T cells. Implications for the recruitment of inflammatory cells to damaged epithelia. J. Immunol 157:3 (1996), 985–992.
70. [70] Matsue, H., Bergstresser, P.R., Takashima, A., Reciprocal cytokine-mediated cellular interactions in mouse epidermis: promotion of γ δ T-cell growth by IL-7 and TNFα and inhibition of keratinocyte growth by γIFN. J. Invest. Dermatol 101:4 (1993), 543–548.
71. [71] Carding, S.R., Allan, W., McMickle, A., Doherty, P.C., Activation of cytokine genes in T cells during primary and secondary murine influenza pneumonia. J. Exp. Med 177:2 (1993), 475–482.
72. [72] Lockhart, E., Green, A.M., Flynn, J.L., IL-17 production is dominated by γδ T cells rather than CD4 T cells during Mycobacterium tuberculosis infection. J. Immunol 177:7 (2006), 4662–4669.
73. [73] Pociask, D.A., Chen, K., Choi, S.M., Oury, T.D., Steele, C., Kolls, J.K., γδ T cells attenuate bleomycin-induced fibrosis through the production of CXCL10. Am. J. Pathol 178:3 (2011), 1167–1176.
74. [74] Shibata, K., Yamada, H., Hara, H., Kishihara, K., Yoshikai, Y., Resident Vδ1+ γδ T cells control early infiltration of neutrophils after Escherichia coli infection via IL-17 production. J. Immunol 178:7 (2007), 4466–4472.
75. [75] Tagawa, T., Nishimura, H., Yajima, T., Hara, H., Kishihara, K., Matsuzaki, G., et al. Vδ1+ γδ T cells producing CC chemokines may bridge a gap between neutrophils and macrophages in innate immunity during Escherichia coli infection in mice. J. Immunol 173:8 (2004), 5156–5164.
76. [76] Hudspeth, K., Fogli, M., Correia, D.V., Mikulak, J., Roberto, A., Della Bella, S., et al. Engagement of NKp30 on Vδ1 T cells induces the production of CCL3, CCL4, and CCL5 and suppresses HIV-1 replication. Blood 119:17 (2012), 4013–4016.
77. [77] Wang, L., Das, H., Kamath, A., Bukowski, J.F., Human Vγ2Vδ2 T cells produce IFN-γ and TNF-α with an on/off/on cycling pattern in response to live bacterial products. J. Immunol 167:11 (2001), 6195–6201.
78. [78] Vermijlen, D., Ellis, P., Langford, C., Klein, A., Engel, R., Willimann, K., et al. Distinct cytokine-driven responses of activated blood γδ T cells: insights into unconventional T cell pleiotropy. J. Immunol 178:7 (2007), 4304–4314.
79. [79] Ebert, L.M., Meuter, S., Moser, B., Homing and function of human skin γδ T cells and NK cells: relevance for tumor surveillance. J. Immunol 176:7 (2006), 4331–4336.
80. [80] Laggner, U., Di Meglio, P., Perera, G.K., Hundhausen, C., Lacy, K.E., Ali, N., et al. Identification of a novel proinflammatory human skin-homing Vγ9Vδ2 T cell subset with a potential role in psoriasis. J. Immunol 187:5 (2011), 2783–2793.
81. [81] Li, H., Luo, K., Pauza, C.D., TNF-alpha is a positive regulatory factor for human Vgamma2 Vdelta2 T cells. J. Immunol 181:10 (2008), 7131–7137 18981134 Pubmed Central PMCID: PMC3753041. Epub 2008/11/05. eng.
82. [82] Wu, X., Zhang, J.Y., Huang, A., Li, Y.Y., Zhang, S., Wei, J., et al. Decreased Vdelta2 gammadelta T cells associated with liver damage by regulation of Th17 response in patients with chronic hepatitis B. J. Infect. Dis 208:8 (2013), 1294–1304 23847059 Epub 2013/07/13. eng.
83. [83] Conti, L., Casetti, R., Cardone, M., Varano, B., Martino, A., Belardelli, F., et al. Reciprocal activating interaction between dendritic cells and pamidronate-stimulated gammadelta T cells: role of CD86 and inflammatory cytokines. J. Immunol 174:1 (2005), 252–260 15611247 Epub 2004/12/22. eng.
84. [84] Spranger, S., Sivan, A., Corrales, L., Gajewski, T.F., Tumor and host factors controlling antitumor immunity and efficacy of cancer immunotherapy. Adv. Immunol 130 (2016), 75–93.
85. [85] van der Burg, S.H., Arens, R., Ossendorp, F., van Hall, T., Melief, C.J., Vaccines for established cancer: overcoming the challenges posed by immune evasion. Nat. Rev. Cancer 16:4 (2016), 219–233.
86. [86] Dai, H., Wang, Y., Lu, X., Han, W., Chimeric antigen receptors modified T-cells for cancer therapy. J. Natl. Cancer Inst, 108(7), 2016, djv439.
87. [87] Maus, M.V., Grupp, S.A., Porter, D.L., June, C.H., Antibody-modified T cells: CARs take the front seat for hematologic malignancies. Blood 123:17 (2014), 2625–2635.
88. [88] Kalos, M., Levine, B.L., Porter, D.L., Katz, S., Grupp, S.A., Bagg, A., et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci. Transl. Med, 3(95), 2011 95ra73.
89. [89] Brentjens, R.J., Rivière, I., Park, J.H., Davila, M.L., Wang, X., Stefanski, J., et al. Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood 118:18 (2011), 4817–4828.
90. [90] Turtle, C.J., Hanafi, L.-A., Berger, C., Gooley, T.A., Cherian, S., Hudecek, M., et al. CD19 CAR–T cells of defined CD4+: CD8+ composition in adult B cell ALL patients. J. Clin. Invest, 126(6), 2016.
91. [91] Morgan, R.A., Yang, J.C., Kitano, M., Dudley, M.E., Laurencot, C.M., Rosenberg, S.A., Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol. Ther 18:4 (2010), 843–851.
92. [92] Lamers, C.H., Sleijfer, S., Vulto, A.G., Kruit, W.H., Kliffen, M., Debets, R., et al. Treatment of metastatic renal cell carcinoma with autologous T-lymphocytes genetically retargeted against carbonic anhydrase IX: first clinical experience. J. Clin. Oncol 24:13 (2006), e20–e22 16648493 Epub 2006/05/02. eng.
93. [93] Petrovic, R.M., Wilkie, S., Maher, J., Abstract A082: developing a PD-1 based inhibitory chimeric antigen receptor (ICAR) for co-expression, to overcome off-tumor toxicity when targeting ErbB2 using engineered T cells. Cancer Immunol. Res, 4(1 Suppl.), 2016, A082.
94. [94] Liu, X., Ranganathan, R., Jiang, S., Fang, C., Sun, J., Kim, S., et al. A Chimeric Switch-Receptor Targeting PD1 Augments the Efficacy of Second-Generation CAR T Cells in Advanced Solid Tumors. Cancer Res 76:6 (2016), 1578–1590.
95. [95] Fedorov, V.D., Themeli, M., Sadelain, M., PD-1- and CTLA-4-based inhibitory chimeric antigen receptors (iCARs) divert off-target immunotherapy responses. Sci. Transl. Med, 5(215), 2013, 215ra172 24337479 Pubmed Central PMCID: PMC4238416. Epub 2013/12/18. eng.
96. [96] Roybal, K.T., Rupp, L.J., Morsut, L., Walker, W.J., McNally, K.A., Park, J.S., et al. Precision tumor recognition by T cells with combinatorial antigen-sensing circuits. Cell 164:4 (2016), 770–779.
97. [97] Kloss, C.C., Condomines, M., Cartellieri, M., Bachmann, M., Sadelain, M., Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells. Nat. Biotechnol 31:1 (2013), 71–75 23242161 Epub 2012/12/18. eng.
98. [98] Craddock, J.A., Lu, A., Bear, A., Pule, M., Brenner, M.K., Rooney, C.M., et al. Enhanced tumor trafficking of GD2 chimeric antigen receptor T cells by expression of the chemokine receptor CCR2b. J. Immunother 33:8 (2010), 780–788 20842059 Pubmed Central PMCID: PMC2998197. Epub 2010/09/16. eng.
99. [99] Moon, E.K., Carpenito, C., Sun, J., Wang, L.C., Kapoor, V., Predina, J., et al. Expression of a functional CCR2 receptor enhances tumor localization and tumor eradication by retargeted human T cells expressing a mesothelin-specific chimeric antibody receptor. Clin. Cancer Res 17:14 (2011), 4719–4730 21610146 Pubmed Central PMCID: PMC3612507. Epub 2011/05/26. eng.
100. [100] Curran, K.J., Seinstra, B.A., Nikhamin, Y., Yeh, R., Usachenko, Y., van Leeuwen, D.G., et al. Enhancing antitumor efficacy of chimeric antigen receptor T cells through constitutive CD40L expression. Mol. Ther 23:4 (2015), 769–778 25582824 Pubmed Central PMCID: PMC4395796. Epub 2015/01/15. eng.
101. [101] Pegram, H.J., Purdon, T.J., van Leeuwen, D.G., Curran, K.J., Giralt, S.A., Barker, J.N., et al. IL-12-secreting CD19-targeted cord blood-derived T cells for the immunotherapy of B-cell acute lymphoblastic leukemia. Leukemia 29:2 (2015), 415–422 25005243 Epub 2014/07/10. eng.
102. [102] Koneru, M., Purdon, T.J., Spriggs, D., Koneru, S., Brentjens, R.J., IL-12 secreting tumor-targeted chimeric antigen receptor T cells eradicate ovarian tumors. Oncoimmunology, 4(3), 2015, e994446 25949921 Pubmed Central PMCID: PMC4404840. Epub 2015/05/08. Eng.
103. [103] Hoyos, V., Savoldo, B., Quintarelli, C., Mahendravada, A., Zhang, M., Vera, J., et al. Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety. Leukemia 24:6 (2010), 1160–1170 20428207 Pubmed Central PMCID: PMC2888148. Epub 2010/04/30. eng.
104. [104] Caruana, I., Savoldo, B., Hoyos, V., Weber, G., Liu, H., Kim, E.S., et al. Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes. Nat. Med 21:5 (2015), 524–529.
105. [105] Till, B.G., Jensen, M.C., Wang, J., Qian, X., Gopal, A.K., Maloney, D.G., et al. CD20-specific adoptive immunotherapy for lymphoma using a chimeric antigen receptor with both CD28 and 4-1BB domains: pilot clinical trial results. Blood 119:17 (2012), 3940–3950.
106. [106] Schultze, J.L., Nadler, L.M., T cell mediated immunotherapy for B cell lymphoma. J. Mol. Med 77:3 (1999), 322–331.
107. [107] Girardi, M., Oppenheim, D.E., Steele, C.R., Lewis, J.M., Glusac, E., Filler, R., et al. Regulation of cutaneous malignancy by γδ T cells. Science 294:5542 (2001), 605–609.
108. [108] Liu, Z., Eltoum, I.-E.A., Guo, B., Beck, B.H., Cloud, G.A., Lopez, R.D., Protective immunosurveillance and therapeutic antitumor activity of γδ T cells demonstrated in a mouse model of prostate cancer. J. Immunol 180:9 (2008), 6044–6053.
109. [109] Zhao, X., Wei, Y.-Q., Kariya, Y., Teshigawara, K., Uchida, A., Accumulation of γ/δ T cells in human dysgerminoma and seminoma: roles in autologous tumor killing and granuloma formation. Immunol. Invest 24:4 (1995), 607–618.
110. [110] Todaro, M., D'Asaro, M., Caccamo, N., Iovino, F., Francipane, M.G., Meraviglia, S., et al. Efficient killing of human colon cancer stem cells by γδ T lymphocytes. J. Immunol 182:11 (2009), 7287–7296.
111. [111] D'Asaro, M., La Mendola, C., Di Liberto, D., Orlando, V., Todaro, M., Spina, M., et al. Vγ9Vδ2 T lymphocytes efficiently recognize and kill zoledronate-sensitized, imatinib-sensitive, and imatinib-resistant chronic myelogenous leukemia cells. J. Immunol 184:6 (2010), 3260–3268.
112. [112] Liu, Z., Guo, B.L., Gehrs, B.C., Nan, L., Lopez, R.D., Ex vivo expanded human Vλ9Vδ2+ λδ-T cells mediate innate antitumor activity against human prostate cancer cells in vitro. J. Urol 173:5 (2005), 1552–1556.
113. [113] Maeurer, M.J., Human Intestinal V81+ T Lymphocytes Recognize Tumor Cells of Epithelial Origin. 1996.
114. [114] Viey, E., Fromont, G., Escudier, B., Morel, Y., Da Rocha, S., Chouaib, S., et al. Phosphostim-activated γδ T cells kill autologous metastatic renal cell carcinoma. J. Immunol 174:3 (2005), 1338–1347.
115. [115] Corvaisier, M., Moreau-Aubry, A., Diez, E., Bennouna, J., Mosnier, J.-F., Scotet, E., et al. Vγ9Vδ2 T cell response to colon carcinoma cells. J. Immunol 175:8 (2005), 5481–5488.
116. [116] Xu, C., Zhang, H., Hu, H., He, H., Wang, Z., Xu, Y., et al. γδ T cells recognize tumor cells via CDR3δ region. Mol. Immunol 44:4 (2007), 302–310.
117. [117] Lamb, L.S. Jr., Henslee-Downey, P.J., Parrish, R.S., Godder, K., Thompson, J., Lee, C., et al. Rapid communication: increased frequency of TCRγδ+ T cells in disease-free survivors following t cell-depleted, partially mismatched, related donor bone marrow transplantation for leukemia. J. Hematother 5:5 (1996), 503–509.
118. [118] Godder, K., Henslee-Downey, P., Mehta, J., Park, B., Chiang, K., Abhyankar, S., et al. Long term disease-free survival in acute leukemia patients recovering with increased γδ T cells after partially mismatched related donor bone marrow transplantation. Bone Marrow Transplant 39:12 (2007), 751–757.
119. [119] Devaud, C., Bilhere, E., Loizon, S., Pitard, V., Behr, C., Moreau, J.F., et al. Antitumor activity of gammadelta T cells reactive against cytomegalovirus-infected cells in a mouse xenograft tumor model. Cancer Res 69:9 (2009), 3971–3978 19383918 Epub 2009/04/23. eng.
120. [120] Wilhelm, M., Smetak, M., Schaefer-Eckart, K., Kimmel, B., Birkmann, J., Einsele, H., et al. Successful adoptive transfer and in vivo expansion of haploidentical γδ T cells. J. Transl. Med, 12(45), 2014, 1186.
121. [121] Izumi, T., Kondo, M., Takahashi, T., Fujieda, N., Kondo, A., Tamura, N., et al. Ex vivo characterization of γδ T-cell repertoire in patients after adoptive transfer of Vγ9Vδ2 T cells expressing the interleukin-2 receptor β-chain and the common γ-chain. Cytotherapy 15:4 (2013), 481–491.
122. [122] Kunzmann, V., Smetak, M., Kimmel, B., Weigang-Koehler, K., Goebeler, M., Birkmann, J., et al. Tumor-promoting versus tumor-antagonizing roles of γδ T cells in cancer immunotherapy: results from a prospective phase I/II trial. J. Immunother 35:2 (2012), 205–213.
123. [123] Nicol, A., Tokuyama, H., Mattarollo, S., Hagi, T., Suzuki, K., Yokokawa, K., et al. Clinical evaluation of autologous gamma delta T cell-based immunotherapy for metastatic solid tumours. Br. J. Cancer 105:6 (2011), 778–786.
124. [124] Corvaisier, M., Moreau-Aubry, A., Diez, E., Bennouna, J., Mosnier, J.F., Scotet, E., et al. V gamma 9V delta 2 T cell response to colon carcinoma cells. J. Immunol 175:8 (2005), 5481–5488 16210656 Epub 2005/10/08. eng.
125. [125] Bendle, G.M., Haanen, J.B., Schumacher, T.N., Preclinical development of T cell receptor gene therapy. Curr. Opin. Immunol 21:2 (2009), 209–214.
126. [126] van der Veken, L.T., Coccoris, M., Swart, E., Falkenburg, J.H., Schumacher, T.N., Heemskerk, M.H., Alpha beta T cell receptor transfer to gamma delta T cells generates functional effector cells without mixed TCR dimers in vivo. J. Immunol 182:1 (2009), 164–170 19109147 Epub 2008/12/26. eng.
127. [127] van der Veken, L.T., Hagedoorn, R.S., van Loenen, M.M., Willemze, R., Falkenburg, J.F., Heemskerk, M.H., αβ T-cell receptor engineered γδ T cells mediate effective antileukemic reactivity. Cancer Res 66:6 (2006), 3331–3337.
128. [128] Hiasa, A., Nishikawa, H., Hirayama, M., Kitano, S., Okamoto, S., Chono, H., et al. Rapid αβ TCR-mediated responses in γδ T cells transduced with cancer-specific TCR genes. Gene Ther 16:5 (2009), 620–628.
129. [129] Rischer, M., Pscherer, S., Duwe, S., Vormoor, J., Jurgens, H., Rossig, C., Human gammadelta T cells as mediators of chimaeric-receptor redirected anti-tumour immunity. Br. J. Haematol 126:4 (2004), 583–592 15287953 Epub 2004/08/04. eng.
130. [130] Peng, G., Wang, H.Y., Peng, W., Kiniwa, Y., Seo, K.H., Wang, R.-F., Tumor-infiltrating γδ T cells suppress T and dendritic cell function via mechanisms controlled by a unique toll-like receptor signaling pathway. Immunity 27:2 (2007), 334–348.
131. [131] Hua, F., Kang, N., Gao, Y.A., Cui, L.X., Ba, D.N., He, W., Potential regulatory role of in vitro-expanded Vdelta1 T cells from human peripheral blood. Immunol. Res 56:1 (2013), 172–180 23532670 Epub 2013/03/28. eng.
132. [132] Traxlmayr, M.W., Wesch, D., Dohnal, A.M., Funovics, P., Fischer, M.B., Kabelitz, D., et al. Immune suppression by gammadelta T-cells as a potential regulatory mechanism after cancer vaccination with IL-12 secreting dendritic cells. J. Immunother 33:1 (2010), 40–52 19952957 Epub 2009/12/03. eng.
133. [133] Lopez, R.D., Xu, S., Guo, B., Negrin, R.S., Waller, E.K., CD2-mediated IL-12–dependent signals render human γδ-T cells resistant to mitogen-induced apoptosis, permitting the large-scale ex vivo expansion of functionally distinct lymphocytes: implications for the development of adoptive immunotherapy strategies. Blood 96:12 (2000), 3827–3837.
134. [134] Siegers, G.M., Ribot, E.J., Keating, A., Foster, P.J., Extensive expansion of primary human gamma delta T cells generates cytotoxic effector memory cells that can be labeled with Feraheme for cellular MRI. Cancer Immunol. Immunother 62:3 (2013), 571–583.
135. [135] Lamb, L., Musk, P., Ye, Z., van Rhee, F., Geier, S., Tong, J., et al. Human γδ+ T lymphocytes have in vitro graft vs leukemia activity in the absence of an allogeneic response. Bone Marrow Transplant, 27(6), 2001.
136. [136] Rincon-Orozco, B., Kunzmann, V., Wrobel, P., Kabelitz, D., Steinle, A., Herrmann, T., Activation of Vγ9Vδ2 T cells by NKG2D. J. Immunol 175:4 (2005), 2144–2151.
137. [137] Nitahara, A., Shimura, H., Ito, A., Tomiyama, K., Ito, M., Kawai, K., NKG2D ligation without T cell receptor engagement triggers both cytotoxicity and cytokine production in dendritic epidermal T cells. J. Invest. Dermatol 126:5 (2006), 1052–1058.
138. [138] Bacon, L., Eagle, R.A., Meyer, M., Easom, N., Young, N.T., Trowsdale, J., Two human ULBP/RAET1 molecules with transmembrane regions are ligands for NKG2D. J. Immunol 173:2 (2004), 1078–1084.
139. [139] Devine, L., Rogozinski, L., Naidenko, O.V., Cheroutre, H., Kavathas, P.B., The complementarity-determining region-like loops of CD8α interact differently with β2-microglobulin of the class I molecules H-2Kb and thymic leukemia antigen, while similarly with their α3 domains. J. Immunol 168:8 (2002), 3881–3886.
140. [140] Liu, Y., Xiong, Y., Naidenko, O.V., Liu, J.-H., Zhang, R., Joachimiak, A., et al. The crystal structure of a TL/CD8αα complex at 2.1 Å resolution: implications for modulation of T cell activation and memory. Immunity 18:2 (2003), 205–215.
141. [141] Fahrer, A.M., Konigshofer, Y., Kerr, E.M., Ghandour, G., Mack, D.H., Davis, M.M., et al. Attributes of γδ intraepithelial lymphocytes as suggested by their transcriptional profile. Proc. Natl. Acad. Sci. U.S.A. 98:18 (2001), 10261–10266.
142. [142] Shires, J., Theodoridis, E., Hayday, A.C., Biological insights into TCRγδ+ and TCRαβ+ intraepithelial lymphocytes provided by serial analysis of gene expression (SAGE). Immunity 15:3 (2001), 419–434.
143. [143] Dasgupta, S., Bhattacharya-Chatterjee, M., O'Malley, B.W., Chatterjee, S.K., Inhibition of NK cell activity through TGF-β1 by down-regulation of NKG2D in a murine model of head and neck cancer. J. Immunol 175:8 (2005), 5541–5550.
144. [144] Li, K., Mandai, M., Hamanishi, J., Matsumura, N., Suzuki, A., Yagi, H., et al. Clinical significance of the NKG2D ligands, MICA/B and ULBP2 in ovarian cancer: high expression of ULBP2 is an indicator of poor prognosis. Cancer Immunol. Immunother 58:5 (2009), 641–652.
145. [145] Galon, J., Costes, A., Sanchez-Cabo, F., Kirilovsky, A., Mlecnik, B., Lagorce-Pagès, C., et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313:5795 (2006), 1960–1964.
146. [146] Kim, S.T., Jeong, H., Woo, O.H., Seo, J.H., Kim, A., Lee, E.S., et al. Tumor-infiltrating lymphocytes, tumor characteristics, and recurrence in patients with early breast cancer. Am. J. Clin. Oncol 36:3 (2013), 224–231.
147. [147] Piersma, S.J., Jordanova, E.S., van Poelgeest, M.I., Kwappenberg, K.M., van der Hulst, J.M., Drijfhout, J.W., et al. High number of intraepithelial CD8+ tumor-infiltrating lymphocytes is associated with the absence of lymph node metastases in patients with large early-stage cervical cancer. Cancer Res 67:1 (2007), 354–361.
148. [148] Kmiecik, J., Poli, A., Brons, N.H., Waha, A., Eide, G.E., Enger, P.Ø., et al. Elevated CD3+ and CD8+ tumor-infiltrating immune cells correlate with prolonged survival in glioblastoma patients despite integrated immunosuppressive mechanisms in the tumor microenvironment and at the systemic level. J. Neuroimmunol 264:1 (2013), 71–83.
149. [149] Mabuchi, T., Singh, T.P., Takekoshi, T., Jia, G.-F., Wu, X., Kao, M.C., et al. CCR6 is required for epidermal trafficking of γδ-T cells in an IL-23-induced model of psoriasiform dermatitis. J. Invest. Dermatol 133:1 (2013), 164–171.
150. [150] Cepek, K.L., Shaw, S.K., Parker, C.M., Russell, G.J., Morrow, J.S., Rimm, D.L., et al. Adhesion between epithelial cells and T lymphocytes mediated by E-cadherin and the αEβ7 integrin. 1994.
151. [151] Cerf-Bensussan, N., Schneeberger, E.E., Bhan, A.K., Immunohistologic and immunoelectron microscopic characterization of the mucosal lymphocytes of human small intestine by the use of monoclonal antibodies. J. Immunol 130:6 (1983), 2615–2622 6687894 Epub 1983/06/01. eng.
152. [152] Beck, B.H., Kim, H.-G., Kim, H., Samuel, S., Liu, Z., Shrestha, R., et al. Adoptively transferred ex vivo expanded γδ-T cells mediate in vivo antitumor activity in preclinical mouse models of breast cancer. Breast Cancer Res. Treat 122:1 (2010), 135–144.
153. [153] Brandes, M., Willimann, K., Lang, A.B., Nam, K.-H., Jin, C., Brenner, M.B., et al. Flexible migration program regulates γδ T-cell involvement in humoral immunity. Blood 102:10 (2003), 3693–3701.
154. [154] Orimo, A., Gupta, P.B., Sgroi, D.C., Arenzana-Seisdedos, F., Delaunay, T., Naeem, R., et al. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 121:3 (2005), 335–348.
155. [155] Heidemann, J., Ogawa, H., Rafiee, P., Lügering, N., Maaser, C., Domschke, W., et al. Mucosal angiogenesis regulation by CXCR4 and its ligand CXCL12 expressed by human intestinal microvascular endothelial cells. Am. J. Physiol. Gastrointest. Liver Physiol 286:6 (2004), G1059–G1068.
156. [156] Gray, E.E., Suzuki, K., Cyster, J.G., Cutting edge: identification of a motile IL-17–producing γδ T cell population in the dermis. J. Immunol 186:11 (2011), 6091–6095.
157. [157] Sumaria, N., Roediger, B., Ng, L.G., Qin, J., Pinto, R., Cavanagh, L.L., et al. Cutaneous immunosurveillance by self-renewing dermal γδ T cells. J. Exp. Med 208:3 (2011), 505–518.
158. [158] Ma, Y., Aymeric, L., Locher, C., Mattarollo, S.R., Delahaye, N.F., Pereira, P., et al. Contribution of IL-17–producing γδ T cells to the efficacy of anticancer chemotherapy. J. Exp. Med 208:3 (2011), 491–503.
159. [159] Singh, N., Perazzelli, J., Grupp, S.A., Barrett, D.M., Early memory phenotypes drive T cell proliferation in patients with pediatric malignancies. Sci. Transl. Med, 8(320), 2016, 320ra3.
160. [160] Ribot, J.C., Mancio-Silva, L., Pamplona, A., Silva-Santos, B., B7–CD28 costimulatory signals control the survival and proliferation of murine and human γδ T cells via IL-2 production. J. Immunol 189:3 (2012), 1202–1208.
161. [161] deBarros, A., Chaves-Ferreira, M., d'Orey, F., Ribot, J.C., Silva-Santos, B., CD70–CD27 interactions provide survival and proliferative signals that regulate T cell receptor-driven activation of human γδ peripheral blood lymphocytes. Eur. J. Immunol 41:1 (2011), 195–201.
162. [162] Maniar, A., Zhang, X., Lin, W., Gastman, B.R., Pauza, C.D., Strome, S.E., et al. Human γδ T lymphocytes induce robust NK cell–mediated antitumor cytotoxicity through CD137 engagement. Blood 116:10 (2010), 1726–1733.
163. [163] Song, D.G., Ye, Q., Poussin, M., Harms, G.M., Figini, M., Powell, D.J. Jr., CD27 costimulation augments the survival and antitumor activity of redirected human T cells in vivo. Blood 119:3 (2012), 696–706 22117050 Epub 2011/11/26. eng.
164. [164] Zou, W., Regulatory T cells, tumour immunity and immunotherapy. Nat. Rev. Immunol 6:4 (2006), 295–307.