Targeting the TCR signaling checkpoint: A therapeutic strategy to reactivate memory T cells in the tumor microenvironment

Expert Opinion on Therapeutic Targets

Volumn 12, Issue 4, 2008, Pages 477-490

  Simpson Abelson, Michelle R ^a   Bankert, Richard B ^a  

^a UNIVERSITY AT BUFFALO   (United States)

Author keywords

Cancer immunotherapy; Interleukin 12 (IL 12); Memory T cells; T cell receptor signaling pathway (TCR); Transforming growth factor beta 1 (TGF 1); Tumor immunology

Indexed keywords

ANTINEOPLASTIC AGENT; CALMODULIN; CD28 ANTIGEN; CD3 ANTIBODY; CD3 ANTIGEN; GAMMA INTERFERON; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 12; INTERLEUKIN 17; INTERLEUKIN 23; LAT PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE; NANOCARRIER; PROTEIN KINASE ZAP 70; PROTEIN SLP 76; PROTEIN TYROSINE PHOSPHATASE SHP 1; SCAFFOLD PROTEIN; TRANSCRIPTION FACTOR AP 1; TRANSCRIPTION FACTOR NFAT; TRANSFORMING GROWTH FACTOR BETA RECEPTOR 1 INHIBITOR; TRANSFORMING GROWTH FACTOR BETA1; TUMOR ANTIGEN; UNCLASSIFIED DRUG;

ADJUVANT THERAPY; ANTIGEN ANTIBODY COMPLEX; ANTINEOPLASTIC ACTIVITY; CANCER IMMUNIZATION; CANCER IMMUNOTHERAPY; CANCER INHIBITION; CD4+ CD25+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CLINICAL TRIAL; DRUG FORMULATION; DRUG RELEASE; DRUG TARGETING; FIBROSARCOMA; HUMAN; IMMUNE RESPONSE; LOW DRUG DOSE; LUNG NON SMALL CELL CANCER; MEMORY T LYMPHOCYTE; MICROENVIRONMENT; NONHODGKIN LYMPHOMA; NONHUMAN; OVARY CANCER; PANCREAS ADENOCARCINOMA; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; REVIEW; SEVERE COMBINED IMMUNODEFICIENCY; SIGNAL TRANSDUCTION; T LYMPHOCYTE RECEPTOR GENE; TUMOR ASSOCIATED LEUKOCYTE; TUMOR IMMUNITY; ANIMAL; DISEASE COURSE; DRUG DELIVERY SYSTEM; DRUG EFFECT; IMMUNOLOGICAL MEMORY; IMMUNOLOGY; IMMUNOTHERAPY; METABOLISM; NEOPLASM; PHYSIOLOGY; T LYMPHOCYTE;

ANIMALS; ANTIGENS, NEOPLASM; DISEASE PROGRESSION; DRUG DELIVERY SYSTEMS; HUMANS; IMMUNOLOGIC MEMORY; IMMUNOTHERAPY; NEOPLASMS; SIGNAL TRANSDUCTION; T-LYMPHOCYTES;

EID: 42149156220     PISSN: 14728222     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728222.12.4.477     Document Type: Review

References (106)

1. Finn OJ. Cancer vaccines: between the idea and the reality. Nat Rev 2003;3(8):630-41
2. Pardoll D. Does the immune system see tumors as foreign or self? Ann Rev Immunol 2003;21:807-39
3. Melief CJ, Toes RE, Medema JP, et al. Strategies for immunotherapy of cancer. Adv Immunol 2000;75:235-82
4. Khong HT, Restifo NP. Natural selection of tumor variants in the generation of "tumor escape" phenotypes. Nat Immunol 2002;3(11):999-1005
5. Gilboa E. The promise of cancer vaccines. Nat Rev Cancer 2004;4(5):401-11
6. Yee C, Thompson JA, Byrd D, et al. Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T cells. Proc Natl Acad Sci USA 2002;99(25):16168-73
7. June CH. Adoptive T cell therapy for cancer in the clinic. J Clin Invest 2007;117(6):1466-76
8. June CH. Principles of adoptive T cell cancer therapy. J Clin Invest 2007;117(5):1204-12
9. Milone MC, June CH. Adoptive immunotherapy: new ways to skin the cat? Clin Immunol 2005;117(2):101-3
10. Porter DL, Levine BL, Bunin N, et al. A phase 1 trial of donor lymphocyte infusions expanded and activated ex vivo via CD3/CD28 costimulation. Blood 2006;107(4):1325-31
11. Rapoport AP, Stadtmauer EA, Aqui N, et al. Restoration of immunity in lymphopenic individuals with cancer by vaccination and adoptive T-cell transfer. Nat Med 2005;11(11):1230-7
12. Dudley ME, Wunderlich JR, Robbins PF, et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 2002;298(5594):850-4
13. Morgan RA, Dudley ME, Wunderlich JR, et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 2006;314(5796):126-9
14. Kershaw MH, Westwood JA, Parker LL, et al. A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin Cancer Res 2006;12(20 Pt 1):6106-15
15. Boon T, Coulie PG, Van den Eynde BJ, van der Bruggen P. Human T cell responses against melanoma. Ann Rev Immunol 2006;24:175-208
16. Curiel TJ, Coukos G, Zou L, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 2004;10(9):942-9
17. Broderick L, Bankert RB. Memory T cells in human tumor and chronic inflammatory microenvironments: sleeping beauties re-awakened by a cytokine kiss. Immunol Invest 2006;35(3-4):419-36
18. Chiou SH, Sheu BC, Chang WC, et al. Current concepts of tumor-infiltrating lymphocytes in human malignancies. J Reprod Immunol 2005;67(1-2):35-50
19. Zou W. Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer 2005;5(4):263-74
20. Broderick L, Yokota SJ, Reineke J, et al. Human CD4+ effector memory T cells persisting in the microenvironment of lung cancer xenografts are activated by local delivery of IL-12 to proliferate, produce IFN-gamma, and eradicate tumor cells. J Immunol 2005;174(2):898-906
21. Hogan RJ, Usherwood EJ, Zhong W, et al. Activated antigen-specific CD8+ T cells persist in the lungs following recovery from respiratory virus infections. J Immunol 2001;166(3):1813-22
22. Masopust D, Vezys V, Marzo AL, Lefrancois L. Preferential localization of effector memory cells in nonlymphoid tissue. Science 2001;291(5512):2413-7
23. Badovinac VP, Porter BB, Harty JT. Programmed contraction of CD8(+) T cells after infection. Nat Immunol 2002;3(7):619-26
24. Wherry EJ, Barber DL, Kaech SM, et al. Antigen-independent memory CD8 T cells do not develop during chronic viral infection. Proc Natl Acad Sci USA 2004;101(45):16004-9
25. Sprent J, Surh CD. T cell memory. Ann Rev Immunol 2002;20:551-79
26. Mizoguchi H, O'Shea JJ, Longo DL, et al. Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice. Science 1992;258(5089):1795-8
27. Agrawal S, Marques J, Delfau-Larue MH, et al. CD3 hyporesponsiveness and in vitro apoptosis are features of T cells from both malignant and nonmalignant secondary lymphoid organs. J Clin Invest 1998;102(9):1715-23
28. Uzzo RG, Rayman P, Kolenka V, et al. Renal cell carcinoma-derived gangliosides suppress nuclear factor-κB activation in T cells. J Clin Invest 1999;104(6):769-76
29. Weil R, Israel A. Deciphering the pathway from the TCR to NF-κB. Cell Death Differ 2006;13(5):826-33
30. Nel AE. T-cell activation through the antigen receptor. Part 1. Signaling components, signaling pathways, and signal integration at the T-cell antigen receptor synapse. J Allergy Clin Immunol 2002;109(5):758-70
31. Broderick L, Brooks SP, Takita H, et al. IL-12 reverses anergy to T cell receptor triggering in human lung tumor-associated memory T cells. Clin Immunol 2006;118(2-3):159-69
32. Bernstein JM, Broderick L, Parsons RR, Bankert RB. Human nasal polyp microenvironment maintained in viable and functional states as xenografts in SCID mice. Ann Otol Rhinol Laryngol 2006;115(1):65-73
33. Schwartzberg PL, Finkelstein LD, Readinger JA. TEC-family kinases: regulators of T-helper-cell differentiation. Nat Rev Immunol 2005;5(4):284-95
34. Berg LJ, Finkelstein LD, Lucas JA, Schwartzberg PL. Tec family kinases in T lymphocyte development and function. Ann Rev Immunol 2005;23:549-600
35. Nel AE, Slaughter N. T-cell activation through the antigen receptor. Part 2. Role of signaling cascades in T-cell differentiation, anergy, immune senescence, and development of immunotherapy. J Allergy Clin Immunol 2002;109(6):901-15
36. Watson AR, Lee WT. Differences in signaling molecule organization between naive and memory CD4+ T lymphocytes. J Immunol 2004;173(1):33-41
37. Hall SR, Heffernan BM, Thompson NT, Rowan WC. CD4+ CD45RA+ and CD4+ CD45RO+ T cells differ in their TCR-associated signaling responses. Eur J Immunol 1999;29(7):2098-106
38. Chandok MR, Farber DL. Signaling control of memory T cell generation and function. Semin Immunol 2004;16(5):285-93
39. Hussain SF, Anderson CF, Farber DL. Differential SLP-76 expression and TCR-mediated signaling in effector and memory CD4 T cells. J Immunol 2002;168(4):1557-65
40. Chandok MR, Okoye FI, Ndejembi MP, Farber DL. A biochemical signature for rapid recall of memory CD4 T cells. J Immunol 2007;179(6):3689-98
41. Watson AR, Lee WT. Defective T cell receptor-mediated signal transduction in memory CD4 T lymphocytes exposed to superantigen or anti-T cell receptor antibodies. Cell Immunol 2006;242(2):80-90
42. Whiteside T. Down-Regulation of ζ-chain expression in T cells: a biomarker of prognosis of cancer? Cancer Immunol Immunother 2004;53:865-78
43. Rodriguez PC, Ochoa AC. T cell dysfunction in cancer: role of myeloid cells and tumor cells regulating amino acid availability and oxidative stress. Semin Cancer Biol 2006;16(1):66-72
44. + tumor-infiltrating lymphocyte lytic function. J Immunol 2005;174(4):1830-40
45. Hundt M, Tabata H, Jeon MS, et al. Impaired activation and localization of LAT in anergic T cells as a consequence of a selective palmitoylation defect. Immunity 2006;24(5):513-22
46. Olenchock BA, Guo R, Carpenter JH, et al. Disruption of diacylglycerol metabolism impairs the induction of T cell anergy. Nat Immunol 2006;7(11):1174-81
47. Zha Y, Marks R, Ho AW, et al. T cell anergy is reversed by active Ras and is regulated by diacylglycerol kinase-α. Nat Immunol 2006;7(11):1166-73
48. Chen CH, Seguin-Devaux C, Burke NA, et al. Transforming growth factor β blocks Tec kinase phosphorylation, Ca2+ influx, and NFATc translocation causing inhibition of T cell differentiation. J Exp Med 2003;197(12):1689-99
49. Broderick L, Bankert RB. Membrane-associated TGF-β1 inhibits human memory T cell signaling in malignant and nonmalignant inflammatory microenvironments. J Immunol 2006;177(5):3082-8
50. Li MS, S Wan YY, Robertson AL, Flavell RA. Transforming growth factor-β of immune responses. Ann Rev Immunol 2006;24:99-146
51. Wan YY, Flavell RA. Identifying Foxp3-expressing suppressor T cells with a bicistronic reporter. Proc Natl Acad Sci USA 2005;102(14):5126-31
52. Elliott RL, Blobe GC. Role of transforming growth factor beta in human cancer. J Clin Oncol 2005;23(9):2078-93
53. Pardali K, Moustakas A. Actions of TGF-β as tumor suppressor and pro-metastatic factor in human cancer. Biochim Biophys Acta 2007;1775(1):21-62
54. Wrzesinski SH, Wan YY, Flavell RA. Transforming growth factor-β and the immune response: implications for anticancer therapy. Clin Cancer Res 2007;13(18):5262-70
55. Nazareth MR, Broderick L, Simpson-Abelson MR, et al. Characterization of human lung tumor-associated fibroblasts and their ability to modulate the activation of tumor-associated T cells. J Immunol 2007;178(9):5552-62
56. Saunier EF, Akhurst RJ. TGF beta inhibition for cancer therapy. Curr Cancer Drug Targets 2006;6(7):565-78
57. Ahmadzadeh M, Rosenberg SA. TGF-β1 attenuates the acquisition and expression of effector function by tumor antigen-specific human memory CD8 T cells. J Immunol 2005;174(9):5215-23
58. Chiang JY, Jang IK, Hodes R, Gu H. Ablation of Cbl-b provides protection against transplanted and spontaneous tumors. J Clin Invest 2007;117(4):1029-36
59. Wohlfert LA, Callahan MK, Clark RB. Resistance to CD4+CD25+ regulatory T cells and TGF-β in Cbl-b-/- mice. J Immunol 2004;173(2):1059-65
60. Wohlfert LA, Gorelik L, Mittler R, et al. Cutting edge: deficiency in the E3 ubiquitin ligase Cbl-b results ins multifunctional defect in T cell TGF-β sensitivity in vitro and in vivo. J Immunol 2006;176(3):1316-20
61. Li D, Gal I, Vermes C, et al. Cutting edge: Cbl-b: one of the key molecules tuning CD28- and CTLA-4-mediated T cell costimulation. J Immunol 2004;173(12):7135-9
62. Byrne SN, Knox MC, Halliday GM. TGFβ is responsible for skin tumour infiltration by macrophages enabling the tumours to escape immune destruction. Immunol Cell Biol 2007;86(1):92-7
63. Kulkarni AB, Huh CG, Becker D, et al. Transforming growth factor β1 null mutation in mce causes excessive inflammatory response and early death. Proc Natl Acad Sci USA 1993;90(2):770-4
64. Letterio JJ, Roberts AB. Regulation of immune responses by TGF-β. Ann Rev Immunol 1998;16:137-61
65. Shull MM, Ormsby I, Kier AB, et al. Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory disease. Nature 1992;359(6397):693-9
66. Broderick L, Bankert R. Membrane-associated TGF-β1 inhibits human memory T cell signaling in malignant and nonmalignant inflammatory microenvironments. J Immunol 2006;177(5):3082-8
67. Leivonen SK, Kahari VM. Transforming growth factor-β signaling in cancer invasion and metastasis. Int J Cancer 2007;121(10):2119-24
68. Pinkas J, Teicher BA. TGF-β in cancer and as a therapeutic target. Biochem Pharmacol 2006;72(5):523-9
69. Kano MR, Bae Y, Iwata C, et al. Improvement of cancer-targeting therapy, using nanocarriers for intractable solid tumors by inhibition of TGF-β signaling. Proc Natl Acad Sci USA 2007;104(9):3460-5
70. Gaspar NJ, Li L, Kapoun AM, et al. Inhibition of transforming growth factor β signaling reduces pancreatic adenocarcinoma growth and invasiveness. Mol Pharmacol 2007;72(1):152-61
71. Park IK, Shultz LD, Letterio JJ, Gorham JD. TGF-β1 inhibits T-bet induction by IFN-γ in murine CD4+ T cells through the protein tyrosine phosphatase Src homology region 2 domain-containing phosphatase-1. J Immunol 2005;175(9):5666-74
72. Zhang J, Somani AK, Siminovitch KA. Roles of the SHP-1 tyrosine phosphatase in the negative regulation of cell signalling. Semin Immunol 2000;12(4):361-78
73. Kosugi A, Sakakura J, Yasuda K, et al. Involvement of SHP-1 tyrosine phosphatase in TCR-mediated signaling pathways in lipid rafts. Immunity 2001;14(6):669-80
74. Sathish JG, Dolton G, Leroy FG, Matthews RJ. Loss of Src homology region 2 domain-containing protein tyrosine phosphatase-1 increases CD8+ T cell-APC conjugate formation and is associated with enhanced in vivo CTL function. J Immunol 2007;178(1):330-7
75. Chemnitz JM, Parry RV, Nichols KE, et al. SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation. J Immunol 2004;173(2):945-54
76. Trautmann L, Janbazian L, Chomont N, et al. Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. Nat Med 2006;12(10):1198-202
77. Freeman GJ, Wherry EJ, Ahmed R, Sharpe AH. Reinvigorating exhausted HIV-specific T cells via PD-1-PD-1 ligand blockade. J Exp Med 2006;203(10):2223-7
78. Petrovas C, Casazza JP, Brenchley JM, et al. PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection. J Exp Med 2006;203(10):2281-92
79. Barber DL, Wherry EJ, Masopust D, et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 2006;439(7077):682-7
80. Thompson RH, Dong H, Lohse CM, et al. PD-1 is expressed by tumor-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma. Clin Cancer Res 2007;13(6):1757-61
81. Tomlinson MG, Heath VL, Turck CW, et al. SHIP family inositol phosphatases interact with and negatively regulate the Tec tyrosine kinase. J Biol Chem 2004;279(53):55089-96
82. Colombo MP, Trinchieri G. Interleukin-12 in anti-tumor immunity and immunotherapy. Cytokine Growth Factor Rev 2002;13(2):155-68
83. Del Vecchio M, Bajetta E, Canova S, et al. Interleukin-12: biological properties and clinical application. Clin Cancer Res 2007;13(16):4677-85
84. Yoo JK, Cho JH, Lee SW, Sung YC. IL-12 provides proliferation and survival signals to murine CD4+ T cells through phosphatidylinositol 3-kinase/Akt signaling pathway. J Immunol 2002;169(7):3637-43
85. Tatsumi T, Takehara T, Yamaguchi S, et al. Injection of IL-12 gene-transduced dendritic cells into mouse liver tumor lesions activates both innate and acquired immunity. Gene Ther 2007;14(11):863-71
86. King IL, Segal BM. Cutting edge: IL-12 induces CD4+CD25- T cell activation in the presence of T regulatory cells. J Immunol 2005;175(2):641-5
87. Egilmez NK, Hess SD, Chen FA, et al. Human CD4+ effector T cells mediate indirect interleukin-12- and interferon-γ-dependent suppression of autologous HLA-negative lung tumor xenografts in severe combined immunodeficient mice. Cancer Res 2002;62(9):2611-7
88. Kilinc MO, Aulakh KS, Nair RE, et al. Reversing tumor immune suppression with intratumoral IL-12: activation of tumor-associated T effector/ memory cells, induction of T suppressor apoptosis, and infiltration of CD8+ T effectors. J Immunol 2006;177(10):6962-73
89. Hess SD, Egilmez NK, Bailey N, et al. Human CD4+ T cells present within the microenvironment of human lung tumors are mobilized by the local and sustained release of IL-12 to kill tumors in situ by indirect effects of IFN-γ. J Immunol 2003;170(1):400-12
90. Salem ML, Gillanders WE, Kadima AN, et al. Review: novel nonviral delivery approaches for interleukin-12 protein and gene systems: curbing toxicity and enhancing adjuvant activity. J Interferon Cytokine Res 2006;26(9):593-608
91. Lee YS, Kim JH, Choi KJ, et al. Enhanced antitumor effect of oncolytic adenovirus expressing interleukin-12 and B7-1 in an immunocompetent murine model. Clin Cancer Res 2006;12(19):5859-68
92. Tros De Ilarduya C, Bunuales M, Qian C, Duzgunes N. Antitumoral activity of transferrin-lipoplexes carrying the IL-12 gene in the treatment of colon cancer. J Drug Target 2006;14(8):527-35
93. Nair RE, Kilinc MO, Jones SA, Egilmez NK. Chronic immune therapy induces a progressive increase in intratumoral T suppressor activity and a concurrent loss of tumor-specific CD8+ T effectors in her-2/neu transgenic mice bearing advanced spontaneous tumors. J Immunol 2006;176(12):7325-34
94. Hill HC, Conway TF Jr, Sabel MS, et al. Cancer immunotherapy with interleukin 12 and granulocyte-macrophage colony-stimulating factor-encapsulated microspheres: coinduction of innate and adaptive antitumor immunity and cure of disseminated disease. Cancer Res 2002;62(24):7254-63
95. Langowski JL, Kastelein RA, Oft M. Swords into plowshares: IL-23 repurposes tumor immune surveillance. Trends Immunol 2007;28(5):207-12
96. Hoeve MA, Savage ND, de Boer T, et al. Divergent effects of IL-12 and IL-23 on the production of IL-17 by human T cells. Eur J Immunol 2006;36(3):661-70
97. Numasaki M, Fukushi J, Ono M, et al. Interleukin-17 promotes angiogenesis and tumor growth. Blood 2003;101(7):2620-7
98. Kryczek I, Wei S, Zou L, et al. Cutting edge: Th17 and regulatory T cell dynamics and the regulation by IL-2 in the tumor microenvironment. J Immunol 2007;178(11):6730-3
99. Benchetrit F, Ciree A, Vives V, et al. Interleukin-17 inhibits tumor cell growth by means of a T-cell-dependent mechanism. Blood 2002;99(6):2114-21
100. Langowski JL, Zhang X, Wu L, et al. IL-23 promotes tumour incidence and growth. Nature 2006;442(7101):461-5
101. Kaiga T, Sato M, Kaneda H, et al. Systemic administration of IL-23 induces potent antitumor immunity primarily mediated through Th1-type response in association with the endogenously expressed IL-12. J Immunol 2007;178(12):7571-80
102. Numasaki M, Watanabe M, Suzuki T, et al. IL-17 enhances the net angiogenic activity and in vivo growth of human non-small cell lung cancer in SCID mice through promoting CXCR-2-dependent angiogenesis. J Immunol 2005;175(9):6177-89
103. Takahashi H, Numasaki M, Lotze MT, Sasaki H. Interteukin-17 enhances bFGF-, HGF- and VEGF-induced growth of vascular endothelial cells. Immunol Lett 2005;98(2):189-93
104. Rangarajan A, Weinberg RA. Opinion: comparative biology of mouse versus human cells: modelling human cancer in mice. Nat Rev Cancer 2003;3(12):952-9
105. Steinman RM, Mellman I. Immunotherapy: bewitched, bothered, and bewildered no more. Science 2004;305(5681):197-200
106. Nagaraj S, Gupta K, Pisarev V, et al. Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer. Nat Med 2007;13(7):828-35