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γδ T cells as immune effectors against high-grade gliomas

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Abstract

Almost all individuals diagnosed with glioblastoma multiforme (GBM) will die of their disease as no effective therapies exist. Clearly, novel approaches to this problem are needed. Unlike the adaptive αβ T cell-mediated immune response, which requires antigen processing and MHC-restricted peptide display by antigen-presenting cells, γδ T cells can broadly recognize and immediately respond to a variety of MHC-like stress-induced self antigens, many of which are expressed on human GBM cells. Until now, there has been little progress toward clinical application, although several investigators have recently published clinically approvable methods for large-scale ex vivo expansion of functional γδ T cells for therapeutic purposes. This review discusses the biology of γδ T cells with respect to innate immunotherapy of cancer with a focus on GBM, and explores graft engineering techniques in development for the therapeutic use of γδ T cells.

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References

  1. Castro MG, Cowen R, Williamson IK, et al. Current and future strategies for the treatment of malignant brain tumors. Pharmacol Ther. 2003;98:71–108.

    Article  PubMed  CAS  Google Scholar 

  2. Walker PR, Calzascia T, Dietrich PY. All in the head: obstacles for immune rejection of brain tumours. Immunology. 2002;107:28–38.

    Article  PubMed  CAS  Google Scholar 

  3. Miller DW. Immunobiology of the blood–brain barrier. J Neurovirol. 1999;5:570–8.

    Article  PubMed  CAS  Google Scholar 

  4. Weller M, Fontana A. The failure of current immunotherapy for malignant glioma. Tumor-derived TGF-beta, T-cell apoptosis, and the immune privilege of the brain. Brain Res Brain Res Rev. 1995;21:128–51.

    Article  PubMed  CAS  Google Scholar 

  5. Medewar P. Immunity to homologous grafted skin III. The fate of skin homografts transplanted to the brain, the subcutaneous tissue, and the anterior chamber of the eye. Br J Exp Pathol. 1948;29:58–69.

    Google Scholar 

  6. Doolittle ND, Abrey LE, Bleyer WA, et al. New frontiers in translational research in neuro-oncology and the blood–brain barrier: report of the tenth annual Blood–Brain Barrier Disruption Consortium Meeting. Clin Cancer Res. 2005;11:421–8.

    PubMed  Google Scholar 

  7. Read SB, Kulprathipanja NV, Gomez GG, et al. Human alloreactive CTL interactions with gliomas and with those having upregulated HLA expression from exogenous IFN-gamma or IFN-gamma gene modification. J Interferon Cytokine Res. 2003;23:379–93.

    Article  PubMed  CAS  Google Scholar 

  8. Carson MJ, Sutcliffe JG, Campbell IL. Microglia stimulate naive T-cell differentiation without stimulating T-cell proliferation. J Neurosci Res. 1999;55:127–34.

    Article  PubMed  CAS  Google Scholar 

  9. Aloisi F, Ria F, Penna G, Adorini L. Microglia are more efficient than astrocytes in antigen processing and in Th1 but not Th2 cell activation. J Immunol. 1998;160:4671–80.

    PubMed  CAS  Google Scholar 

  10. Karman J, Ling C, Sandor M, Fabry Z. Initiation of immune responses in brain is promoted by local dendritic cells. J Immunol. 2004;173:2353–61.

    PubMed  CAS  Google Scholar 

  11. Quattrocchi KB, Miller CH, Cush S, et al. Pilot study of local autologous tumor infiltrating lymphocytes for the treatment of recurrent malignant gliomas. J Neurooncol. 1999;45:141–57.

    Article  PubMed  CAS  Google Scholar 

  12. Smyth MJ, Strobl SL, Young HA, Ortaldo JR, Ochoa AC. Regulation of lymphokine-activated killer activity and pore-forming protein gene expression in human peripheral blood CD8+ T lymphocytes. Inhibition by transforming growth factor-beta. J Immunol. 1991;146:3289–97.

    PubMed  CAS  Google Scholar 

  13. Inge TH, McCoy KM, Susskind BM, Barrett SK, Zhao G, Bear HD. Immunomodulatory effects of transforming growth factor-beta on T lymphocytes. Induction of CD8 expression in the CTLL-2 cell line and in normal thymocytes. J Immunol. 1992;148:3847–56.

    PubMed  CAS  Google Scholar 

  14. Jachimczak P, Bogdahn U, Schneider J, et al. The effect of transforming growth factor-beta 2-specific phosphorothioate-anti-sense oligodeoxynucleotides in reversing cellular immunosuppression in malignant glioma. J Neurosurg. 1993;78:944–51.

    Article  PubMed  CAS  Google Scholar 

  15. Merchant RE, Ellison MD, Young HF. Immunotherapy for malignant glioma using human recombinant interleukin-2 and activated autologous lymphocytes. A review of pre-clinical and clinical investigations. J Neurooncol. 1990;8:173–88.

    Article  PubMed  CAS  Google Scholar 

  16. Farkkila M, Jaaskelainen J, Kallio M, et al. Randomised, controlled study of intratumoral recombinant gamma-interferon treatment in newly diagnosed glioblastoma. Br J Cancer. 1994;70:138–41.

    PubMed  CAS  Google Scholar 

  17. Mahaley MS Jr, Bertsch L, Cush S, Gillespie GY. Systemic gamma-interferon therapy for recurrent gliomas. J Neurosurg. 1988;69:826–9.

    Article  PubMed  Google Scholar 

  18. Boiardi A, Silvani A, Ruffini PA, et al. Loco-regional immunotherapy with recombinant interleukin-2 and adherent lymphokine-activated killer cells (A-LAK) in recurrent glioblastoma patients. Cancer Immunol Immunother. 1994;39:193–7.

    Article  PubMed  CAS  Google Scholar 

  19. Rainov NG, Kramm CM, Banning U, et al. Immune response induced by retrovirus-mediated HSV-tk/GCV pharmacogene therapy in patients with glioblastoma multiforme. Gene Ther. 2000;7:1853–8.

    Article  PubMed  CAS  Google Scholar 

  20. Yu JS, Liu G, Ying H, Yong WH, Black KL, Wheeler CJ. Vaccination with tumor lysate-pulsed dendritic cells elicits antigen-specific, cytotoxic T-cells in patients with malignant glioma. Cancer Res. 2004;64:4973–9.

    Article  PubMed  CAS  Google Scholar 

  21. Merchant RE, Baldwin NG, Rice CD, Bear HD. Adoptive immunotherapy of malignant glioma using tumor-sensitized T lymphocytes. Neurol Res. 1997;19:145–52.

    PubMed  CAS  Google Scholar 

  22. Plautz GE, Barnett GH, Miller DW, et al. Systemic T cell adoptive immunotherapy of malignant gliomas. J Neurosurg. 1998;89:42–51.

    Article  PubMed  CAS  Google Scholar 

  23. Barba D, Saris SC, Holder C, Rosenberg SA, Oldfield EH. Intratumoral LAK cell and interleukin-2 therapy of human gliomas. J Neurosurg. 1989;70:175–82.

    Article  PubMed  CAS  Google Scholar 

  24. Saris SC, Patronas NJ, Rosenberg SA, et al. The effect of intravenous interleukin-2 on brain water content. J Neurosurg. 1989;71:169–74.

    Article  PubMed  CAS  Google Scholar 

  25. Hayes RL, Koslow M, Hiesiger EM, et al. Improved long term survival after intracavitary interleukin-2 and lymphokine-activated killer cells for adults with recurrent malignant glioma. Cancer. 1995;76:840–52.

    Article  PubMed  CAS  Google Scholar 

  26. Dillman RO, Duma CM, Schiltz PM, et al. Intracavitary placement of autologous lymphokine-activated killer (LAK) cells after resection of recurrent glioblastoma. J Immunother. 2004;27:398–404.

    Article  PubMed  Google Scholar 

  27. Kruse CA, Cepeda L, Owens B, Johnson SD, Stears J, Lillehei KO. Treatment of recurrent glioma with intracavitary alloreactive cytotoxic T lymphocytes and interleukin-2. Cancer Immunol Immunother. 1997;45:77–87.

    Article  PubMed  CAS  Google Scholar 

  28. Komatsu F, Kajiwara M. CD18/CD54(+CD102), CD2/CD58 pathway-independent killing of lymphokine-activated killer (LAK) cells against glioblastoma cell lines T98G and U373MG. Oncol Res. 2000;12:17–24.

    PubMed  CAS  Google Scholar 

  29. Wischhusen J, Friese MA, Mittelbronn M, Meyermann R, Weller M. HLA-E protects glioma cells from NKG2D-mediated immune responses in vitro: implications for immune escape in vivo. J Neuropathol Exp Neurol. 2005;64:523–8.

    PubMed  CAS  Google Scholar 

  30. Wiendl H, Mitsdoerffer M, Hofmeister V, et al. A functional role of HLA-G expression in human gliomas: an alternative strategy of immune escape. J Immunol. 2002;168:4772–80.

    PubMed  CAS  Google Scholar 

  31. Medzhitov R, Janeway CA Jr. Decoding the patterns of self and nonself by the innate immune system. Science. 2002;296:298–300.

    Article  PubMed  CAS  Google Scholar 

  32. Wu A, Wiesner S, Xiao J, et al. Expression of MHC I and NK ligands on human CD133+ glioma cells: possible targets of immunotherapy. J Neurooncol. 2007;83:121–31.

    Article  PubMed  CAS  Google Scholar 

  33. Friese MA, Platten M, Lutz SZ, et al. MICA/NKG2D-mediated immunogene therapy of experimental gliomas. Cancer Res. 2003;63:8996–9006.

    PubMed  CAS  Google Scholar 

  34. Girardi M, Oppenheim DE, Steele CR, et al. Regulation of cutaneous malignancy by gammadelta T cells. Science. 2001;294:605–9.

    Article  PubMed  CAS  Google Scholar 

  35. Kaminski MJ, Cruz PD Jr, Bergstresser PR, Takashima A. Killing of skin-derived tumor cells by mouse dendritic epidermal T-cells. Cancer Res. 1993;53:4014–9.

    PubMed  CAS  Google Scholar 

  36. Groh V, Steinle A, Bauer S, Spies T. Recognition of stress-induced MHC molecules by intestinal epithelial gammadelta T cells. Science. 1998;279:1737–40.

    Article  PubMed  CAS  Google Scholar 

  37. Wu J, Groh V, Spies T. T cell antigen receptor engagement and specificity in the recognition of stress-inducible MHC class I-related chains by human epithelial gamma delta T cells. J Immunol. 2002;169:1236–40.

    PubMed  CAS  Google Scholar 

  38. Morita CT, Mariuzza RA, Brenner MB. Antigen recognition by human gamma delta T cells: pattern recognition by the adaptive immune system. Springer Semin Immunopathol. 2000;22:191–217.

    Article  PubMed  CAS  Google Scholar 

  39. Bauer S, Groh V, Wu J, et al. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA [see comments]. Science. 1999;285:727–9.

    Article  PubMed  CAS  Google Scholar 

  40. Groh V, Rhinehart R, Secrist H, Bauer S, Grabstein KH, Spies T. Broad tumor-associated expression and recognition by tumor-derived gamma delta T cells of MICA and MICB. Proc Natl Acad Sci USA. 1999;96:6879–84.

    Article  PubMed  CAS  Google Scholar 

  41. Castriconi R, Daga A, Dondero A, et al. NK cells recognize and kill human glioblastoma cells with stem cell-like properties. J Immunol. 2009;182:3530–9.

    Article  PubMed  CAS  Google Scholar 

  42. Vaquero J, Coca S, Oya S, Martinez R, Ramiro J, Salazar FG. Presence and significance of NK cells in glioblastomas. J Neurosurg. 1989;70:728–31.

    Article  PubMed  CAS  Google Scholar 

  43. Friese MA, Wischhusen J, Wick W, et al. RNA interference targeting transforming growth factor-beta enhances NKG2D-mediated antiglioma immune response, inhibits glioma cell migration and invasiveness, and abrogates tumorigenicity in vivo. Cancer Res. 2004;64:7596–603.

    Article  PubMed  CAS  Google Scholar 

  44. Eisele G, Wischhusen J, Mittelbronn M, et al. TGF-beta and metalloproteinases differentially suppress NKG2D ligand surface expression on malignant glioma cells. Brain. 2006;129:2416–25.

    Article  PubMed  Google Scholar 

  45. Hayday AC. [gamma][delta] cells: a right time and a right place for a conserved third way of protection. Annu Rev Immunol. 2000;18:975–1026.

    Article  PubMed  CAS  Google Scholar 

  46. Boismenu R, Havran WL. An innate view of gamma delta T cells. Curr Opin Immunol. 1997;9:57–63.

    Article  PubMed  CAS  Google Scholar 

  47. Strominger JL. The gamma delta T cell receptor and class Ib MHC-related proteins: enigmatic molecules of immune recognition. Cell. 1989;57:895–8.

    Article  PubMed  CAS  Google Scholar 

  48. Carding SR, Egan PJ. Gammadelta T cells: functional plasticity and heterogeneity. Nat Rev Immunol. 2002;2:336–45.

    Article  PubMed  CAS  Google Scholar 

  49. McVay LD, Carding SR. Generation of human gammadelta T-cell repertoires. Crit Rev Immunol. 1999;19:431–60.

    PubMed  CAS  Google Scholar 

  50. Hacker G, Kromer S, Falk M, Heeg K, Wagner H, Pfeffer K. V delta 1+ subset of human gamma delta T cells responds to ligands expressed by EBV-infected Burkitt lymphoma cells and transformed B lymphocytes. J Immunol. 1992;149:3984–9.

    PubMed  CAS  Google Scholar 

  51. Liu Z, Eltoum IE, Guo B, Beck BH, Cloud GA, Lopez RD. Protective immunosurveillance and therapeutic antitumor activity of gammadelta T cells demonstrated in a mouse model of prostate cancer. J Immunol. 2008;180:6044–53.

    PubMed  CAS  Google Scholar 

  52. Ferrarini M, Pupa SM, Zocchi MR, Rugarli C, Menard S. Distinct pattern of HSP72 and monomeric laminin receptor expression in human lung cancers infiltrated by gamma/delta T lymphocytes. Int J Cancer. 1994;57:486–90.

    Article  PubMed  CAS  Google Scholar 

  53. Choudhary A, Davodeau F, Moreau A, Peyrat MA, Bonneville M, Jotereau F. Selective lysis of autologous tumor cells by recurrent gamma delta tumor-infiltrating lymphocytes from renal carcinoma. J Immunol. 1995;154:3932–40.

    PubMed  CAS  Google Scholar 

  54. Zhao X, Wei YQ, Kariya Y, Teshigawara K, Uchida A. Accumulation of gamma/delta T cells in human dysgerminoma and seminoma: roles in autologous tumor killing and granuloma formation. Immunol Invest. 1995;24:607–18.

    Article  PubMed  CAS  Google Scholar 

  55. Bagot M, Heslan M, Dubertret L, Roujeau JC, Tourine R, Levy JP. Antigen-presenting properties of human epidermal cells compared with peripheral blood mononuclear cells. Br J Dermatol. 1985;113(suppl 28):55.

    Article  PubMed  Google Scholar 

  56. Arden B, Clark SP, Kabelitz D, Mak TW. Human T-cell receptor variable gene segment families. Immunogenetics. 1995;42:455–500.

    PubMed  CAS  Google Scholar 

  57. Morita CT, Beckman EM, Bukowski JF, et al. Direct presentation of nonpeptide prenyl pyrophosphate antigens to human gamma delta T cells. Immunity. 1995;3:495–507.

    Article  PubMed  CAS  Google Scholar 

  58. Bukowski JF, Morita CT, Brenner MB. Human gamma delta T cells recognize alkylamines derived from microbes, edible plants, and tea: implications for innate immunity. Immunity. 1999;11:57–65.

    Article  PubMed  CAS  Google Scholar 

  59. Kunzmann V, Bauer E, Feurle J, Weissinger F, Tony HP, Wilhelm M. Stimulation of gammadelta T cells by aminobisphosphonates and induction of antiplasma cell activity in multiple myeloma. Blood. 2000;96:384–92.

    PubMed  CAS  Google Scholar 

  60. Miyagawa F, Tanaka Y, Yamashita S. et al. Essential contribution of germline-encoded lysine residues in Jgamma1.2 segment to the recognition of nonpeptide antigens by human gammadelta T cells. J Immunol. 2001;167:6773–9.

    PubMed  CAS  Google Scholar 

  61. Fisch P, Malkovsky M, Kovats S, et al. Recognition by human V gamma 9/V delta 2 T cells of a GroEL homolog on Daudi Burkitt’s lymphoma cells. Science. 1990;250:1269–73.

    Article  PubMed  CAS  Google Scholar 

  62. Bukowski JF, Morita CT, Tanaka Y, Bloom BR, Brenner MB, Band H. V gamma 2 V delta 2 TCR-dependent recognition of non-peptide antigens and Daudi cells analyzed by TCR gene transfer. J Immunol. 1995;154:998–1006.

    PubMed  CAS  Google Scholar 

  63. Yamaguchi T, Fujimiya Y, Suzuki Y, Katakura R, Ebina T. A simple method for the propagation and purification of gamma delta T cells from the peripheral blood of glioblastoma patients using solid-phase anti-CD3 antibody and soluble IL-2. J Immunol Methods. 1997;205:19–28.

    Article  PubMed  CAS  Google Scholar 

  64. Yamaguchi T, Suzuki Y, Katakura R, Ebina T, Yokoyama J, Fujimiya Y. Interleukin-15 effectively potentiates the in vitro tumor-specific activity and proliferation of peripheral blood gammadeltaT cells isolated from glioblastoma patients. Cancer Immunol Immunother. 1998;47:97–103.

    Article  PubMed  CAS  Google Scholar 

  65. Schilbach KE, Geiselhart A, Wessels JT, Niethammer D, Handgretinger R. Human gammadelta T lymphocytes exert natural and IL-2-induced cytotoxicity to neuroblastoma cells. J Immunother. 2000;23:536–48.

    Article  PubMed  CAS  Google Scholar 

  66. Ferrarini M, Ferrero E, Dagna L, Poggi A, Zocchi MR. Human gammadelta T cells: a nonredundant system in the immune-surveillance against cancer. Trends Immunol. 2002;23:14–8.

    Article  PubMed  CAS  Google Scholar 

  67. Leca G, Vita N, Maiza H, Fasseu M, Bensussan A. A monoclonal antibody to the Hodgkin’s disease-associated antigen CD30 induces activation and long-term growth of human autoreactive gamma delta T cell clone. Cell Immunol. 1994;156:230–9.

    Article  PubMed  CAS  Google Scholar 

  68. Wilhelm M, Kunzmann V, Eckstein S, et al. Gammadelta T cells for immune therapy of patients with lymphoid malignancies. Blood. 2003;102:200–6.

    Article  PubMed  CAS  Google Scholar 

  69. Bonneville M, Scotet E. Human Vgamma9Vdelta2 T cells: promising new leads for immunotherapy of infections and tumors. Curr Opin Immunol. 2006;18:539–46.

    Article  PubMed  CAS  Google Scholar 

  70. Gober HJ, Kistowska M, Angman L, Jeno P, Mori L, De Libero G. Human T cell receptor gammadelta cells recognize endogenous mevalonate metabolites in tumor cells. J Exp Med. 2003;197:163–8.

    Article  PubMed  CAS  Google Scholar 

  71. Tanaka Y, Morita CT, Nieves E, Brenner MB, Bloom BR. Natural and synthetic non-peptide antigens recognized by human gamma delta T cells. Nature. 1995;375:155–8.

    Article  PubMed  CAS  Google Scholar 

  72. Tanaka Y, Sano S, Nieves E, et al. Nonpeptide ligands for human gamma delta T cells. Proc Natl Acad Sci USA. 1994;91:8175–9.

    Article  PubMed  CAS  Google Scholar 

  73. Poggi A, Carosio R, Fenoglio D, et al. Migration of V delta 1 and V delta 2 T cells in response to CXCR3 and CXCR4 ligands in healthy donors and HIV-1-infected patients: competition by HIV-1 Tat. Blood. 2004;103:2205–13.

    Article  PubMed  CAS  Google Scholar 

  74. Spada FM, Grant EP, Peters PJ, et al. Self-recognition of CD1 by gamma/delta T cells: implications for innate immunity. J Exp Med. 2000;191:937–48.

    Article  PubMed  CAS  Google Scholar 

  75. Leslie DS, Vincent MS, Spada FM, et al. CD1-mediated gamma/delta T cell maturation of dendritic cells. J Exp Med. 2002;196:1575–84.

    Article  PubMed  CAS  Google Scholar 

  76. Ismaili J, Olislagers V, Poupot R, Fournie JJ, Goldman M. Human gamma delta T cells induce dendritic cell maturation. Clin Immunol. 2002;103:296–302.

    Article  PubMed  CAS  Google Scholar 

  77. Dolstra H, Fredrix H, van der Meer A, de Witte T, Figdor C, van de Wiel-van Kemenade E. TCR gamma delta cytotoxic T lymphocytes expressing the killer cell-inhibitory receptor p58.2 (CD158b) selectively lyse acute myeloid leukemia cells. Bone Marrow Transplant. 2001;27:1087–93.

    Article  PubMed  CAS  Google Scholar 

  78. Duval M, Yotnda P, Bensussan A, et al. Potential antileukemic effect of gamma delta T cells in acute lymphoblastic leukemia. Leukemia. 1995;9:863–8.

    PubMed  CAS  Google Scholar 

  79. Lamb LS Jr, Musk P, Ye Z, et al. Human gammadelta(+) T lymphocytes have in vitro graft vs leukemia activity in the absence of an allogeneic response. Bone Marrow Transplant. 2001;27:601–6.

    Article  PubMed  Google Scholar 

  80. Lamb LS, Meeh PF, Muga SJ, et al. Gamma delta T cells from acute leukemia patients show restricted CDR3 rearrangements suggestive of a directed immune response. Blood. 2003;11:384a.

    Google Scholar 

  81. Scheurer ME, Bondy ML, Aldape KD, Albrecht T, El-Zein R. Detection of human cytomegalovirus in different histological types of gliomas. Acta Neuropathol. 2008;116:79–86.

    Article  PubMed  CAS  Google Scholar 

  82. Lau SK, Chen YY, Chen WG, et al. Lack of association of cytomegalovirus with human brain tumors. Mod Pathol. 2005;18:838–43.

    Article  PubMed  CAS  Google Scholar 

  83. Cobbs CS, Soroceanu L, Denham S, et al. Human cytomegalovirus induces cellular tyrosine kinase signaling and promotes glioma cell invasiveness. J Neurooncol. 2007;85:271–80.

    Article  PubMed  CAS  Google Scholar 

  84. Mitchell DA, Xie W, Schmittling R, et al. Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma. Neuro Oncol. 2008;10:10–8.

    Article  PubMed  Google Scholar 

  85. Odeberg J, Wolmer N, Falci S, et al. Late human cytomegalovirus (HCMV) proteins inhibit differentiation of human neural precursor cells into astrocytes. J Neurosci Res. 2007;85:583–93.

    Article  PubMed  CAS  Google Scholar 

  86. Dechanet J, Merville P, Berge F, et al. Major expansion of gammadelta T lymphocytes following cytomegalovirus infection in kidney allograft recipients. J Infect Dis. 1999;179:1–8.

    Article  PubMed  CAS  Google Scholar 

  87. Dechanet J, Merville P, Lim A, et al. Implication of gammadelta T cells in the human immune response to cytomegalovirus. J Clin Invest. 1999;103:1437–49.

    Article  PubMed  CAS  Google Scholar 

  88. Pitard V, Roumanes D, Lafarge X, et al. Long-term expansion of effector/memory Vdelta2-gammadelta T cells is a specific blood signature of CMV infection. Blood. 2008;112:1317–24.

    Article  PubMed  CAS  Google Scholar 

  89. Halary F, Pitard V, Dlubek D, et al. Shared reactivity of V{delta}2(neg) {gamma}{delta} T cells against cytomegalovirus-infected cells and tumor intestinal epithelial cells. J Exp Med. 2005;201:1567–78.

    Article  PubMed  CAS  Google Scholar 

  90. Devaud C, Bilhere E, Loizon S, et al. Antitumor activity of gammadelta T cells reactive against cytomegalovirus-infected cells in a mouse xenograft tumor model. Cancer Res. 2009;69:3971–8.

    Article  PubMed  CAS  Google Scholar 

  91. Fujimiya Y, Suzuki Y, Katakura R, et al. In vitro interleukin 12 activation of peripheral blood CD3(+)CD56(+) and CD3(+)CD56(−) gammadelta T cells from glioblastoma patients. Clin Cancer Res. 1997;3:633–43.

    PubMed  CAS  Google Scholar 

  92. Lopez RD, Xu S, Guo B, Negrin RS, Waller EK. CD2-mediated IL-12-dependent signals render human gamma-delta 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. 2000;96:3827–37.

    PubMed  CAS  Google Scholar 

  93. Sato K, Kimura S, Segawa H, et al. Cytotoxic effects of gammadelta T cells expanded ex vivo by a third generation bisphosphonate for cancer immunotherapy. Int J Cancer. 2005;116:94–9.

    Article  PubMed  CAS  Google Scholar 

  94. Watanabe N, Narita M, Yokoyama A, et al. Type I IFN-mediated enhancement of anti-leukemic cytotoxicity of gammadelta T cells expanded from peripheral blood cells by stimulation with zoledronate. Cytotherapy. 2006;8:118–29.

    Article  PubMed  CAS  Google Scholar 

  95. Kunzmann V, Bauer E, Wilhelm M. Gamma/delta T-cell stimulation by pamidronate [letter]. N Engl J Med. 1999;340:737–8.

    Article  PubMed  CAS  Google Scholar 

  96. Salot S, Laplace C, Saiagh S, et al. Large scale expansion of gamma 9 delta 2 T lymphocytes: Innacell gamma delta cell therapy product. J Immunol Methods. 2007;326:63–75.

    Article  PubMed  CAS  Google Scholar 

  97. Bennouna J, Bompas E, Neidhardt EM, et al. Phase-I study of Innacell gammadeltatrade mark, an autologous cell-therapy product highly enriched in gamma9delta2 T lymphocytes, in combination with IL-2, in patients with metastatic renal cell carcinoma. Cancer Immunol Immunother. 2008;57:1599–609.

    Article  PubMed  CAS  Google Scholar 

  98. Kabelitz D, Wesch D, He W. Perspectives of gammadelta T cells in tumor immunology. Cancer Res. 2007;67:5–8.

    Article  PubMed  CAS  Google Scholar 

  99. Guo B, Hollmig K, Lopez RD. Down-regulation of IL-2 receptor a (CD25) characterizes human gd-T cells rendered resistant to apoptosis after CD2 engagement in the presence of IL-12. Cancer Immunol Immunotherapy. 2002;50:625–37.

    Article  CAS  Google Scholar 

  100. Guo B, Hollmig K, Lopez RD. In vitro activity of apoptosis-resistant human gd-T cells against solid malignances. J Clin Oncol. 2001;20:267 (abstract).

    Google Scholar 

  101. Bryant NL, Suarez-Cuervo C, Gillespie G, et al. Characterization and immunotherapeutic potential of γδ T Cells in patients with glioblastoma. Neuro-oncology. 2009;11:357–67.

    Article  PubMed  CAS  Google Scholar 

  102. Russell JH. Activation-induced death of mature T cells in the regulation of immune responses. Curr Opin Immunol. 1995;7:382–8.

    Article  PubMed  CAS  Google Scholar 

  103. Janssen O, Wesselborg S, Heckl-Ostreicher B, et al. T cell receptor/CD3-signaling induces death by apoptosis in human T cell receptor gamma delta+ T cells. J Immunol. 1991;146:35–9.

    PubMed  CAS  Google Scholar 

  104. Ferrarini M, Heltai S, Toninelli E, Sabbadini MG, Pellicciari C, Manfredi AA. Daudi lymphoma killing triggers the programmed death of cytotoxic V gamma 9/V delta 2 T lymphocytes. J Immunol. 1995;154:3704–12.

    PubMed  CAS  Google Scholar 

  105. Argentati K, Re F, Serresi S, et al. Reduced number and impaired function of circulating gamma delta T cells in patients with cutaneous primary melanoma. J Invest Dermatol. 2003;120:829–34.

    Article  PubMed  CAS  Google Scholar 

  106. Meeh PF, King M, O’Brien RL, et al. Characterization of the gammadelta T cell response to acute leukemia. Cancer Immunol Immunother. 2006;55:1072–80.

    Article  PubMed  Google Scholar 

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Acknowledgments

The author gratefully acknowledges the work of Ian Backstrom, Catherine Langford, Dr. Nichole Bryant, and Dr. Suman Bharara in the preparation of figures for this manuscript. Support from the National Institutes of Health NCI Grant P50 CA 097247-06A1 (GYG/JMM), NINDS Grant R21 NS057431-01A1 (LSL), and the Brain Tumor Society Samuel Gershon Leadership Chair (LSL) is also acknowledged and appreciated.

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  1. Division of Hematology and Oncology, University of Alabama at Birmingham, Suite 541 Tinsley Harrison Tower, 1530 Third Avenue South, Birmingham, AL, 35294, USA

    Lawrence S. Lamb Jr.

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Lamb, L.S. γδ T cells as immune effectors against high-grade gliomas. Immunol Res 45, 85–95 (2009). https://doi.org/10.1007/s12026-009-8114-9

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