Tumor-resident CD8+ T-cell: The critical catalyst in IL-12-mediated reversal of tumor immune suppression

Archivum Immunologiae et Therapiae Experimentalis

Volumn 58, Issue 6, 2010, Pages 399-405

  Egilmez, Nejat K ^a   Kilinc, Mehmet O ^a  

^a UNIVERSITY AT BUFFALO   (United States)

Author keywords

CD8+ T cells; IL 12; Immune suppression; Immune therapy; Tumor microenvironment

Indexed keywords

ALPHA INTERFERON; INTERLEUKIN 12; INTERLEUKIN 2;

ADAPTIVE IMMUNITY; ADVANCED CANCER; ANTINEOPLASTIC ACTIVITY; CANCER IMMUNOTHERAPY; CD8+ T LYMPHOCYTE; CYTOTOXIC T LYMPHOCYTE; CYTOTOXICITY; DRUG EFFICACY; EFFECTOR CELL; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; INNATE IMMUNITY; KIDNEY CANCER; MELANOMA; MEMORY CELL; NONHUMAN; PHENOTYPE; REVIEW; SOLID TUMOR; TUMOR REGRESSION;

ANIMALS; CD8-POSITIVE T-LYMPHOCYTES; CYTOTOXICITY, IMMUNOLOGIC; HUMANS; IMMUNOLOGIC MEMORY; IMMUNOTHERAPY; INTERLEUKIN-12; LYMPHOCYTES, TUMOR-INFILTRATING; NEOPLASMS; TUMOR ESCAPE;

EID: 78649326630     PISSN: 0004069X     EISSN: 16614917     Source Type: Journal    
DOI: 10.1007/s00005-010-0097-7     Document Type: Review

References (72)

1. S Agrawal J Marquet M-H Delfau-Larue, et al. 1998 CD3 hyporesponsiveness and in vitro apoptosis are features of T cells from both malignant and nonmalignant secondary lymphoid organs J Clin Invest 102 1715 1723 1:CAS:528:DyaK1cXnt1Oqt70%3D 10.1172/JCI3784 9802885
2. M Ahmadzadeh LA Johnson B Heemskerk, et al. 2009 Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired Blood 114 1537 1544 1:CAS:528:DC%2BD1MXhtVyiur3K 10.1182/blood-2008-12-195792 19423728
3. C Blank A Mackensen 2007 Contribution of the PD-L1/PD-1 pathway to T-cell exhaustion: an update on implications for chronic infections and tumor evasion Cancer Immunol Immunother 56 739 745 10.1007/s00262-006-0272-1 17195077 (Pubitemid 46348742)
4. L Broderick RB Bankert 2006 Membrane-associated TGF-beta1 inhibits human memory T cell signaling in malignant and nonmalignant inflammatory microenvironments J Immunol 177 3082 3088 1:CAS:528:DC%2BD28Xot1Cjsb8%3D 16920945
5. L Broderick RB Bankert 2006 Memory T cells in human tumor and chronic inflammatory microenvironments: sleeping beauties re-awakened by a cytokine kiss Immunol Invest 35 419 436 1:CAS:528:DC%2BD28XpvVCks70%3D 10.1080/ 08820130600755066 16916760 (Pubitemid 44274860)
6. L Broderick SP Brooks H Takita, et al. 2006 IL-12 reverses anergy to T cell receptor triggering in human lung tumor-associated memory T cells Clin Immunol 118 159 169 1:CAS:528:DC%2BD28Xhtlarsrk%3D 10.1016/j.clim.2005.09.008 16271513 (Pubitemid 43199654)
7. V Bronte P Serafini A Mazzoni, et al. 2003 L-arginine metabolism in myeloid cells controls T-lymphocyte functions Trends Immunol 24 302 306 1:CAS:528:DC%2BD3sXks1amsrc%3D 10.1016/S1471-4906(03)00132-7 12810105 (Pubitemid 36694880)
8. MJ Brunda L Luistro RR Warrier, et al. 1993 Antitumor and antimetastatic activity of interleukin 12 against murine tumors J Exp Med 178 1223 1230 1:CAS:528:DyaK3sXlsFyjsL4%3D 10.1084/jem.178.4.1223 8104230
9. F Cavallo P Signorelli M Giovarelli, et al. 1997 Antitumor efficacy of adenocarcinoma cells engineered to produce interleukin 12 (IL-12) or other cytokines compared with exogenous IL-12 J Natl Cancer Inst 89 1049 1058 1:CAS:528:DyaK2sXlt1Cks78%3D 10.1093/jnci/89.14.1049 9230887
10. MA Curran W Montalvo H Yagita, et al. 2010 PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors Proc Natl Acad Sci USA 107 4275 4280 1:CAS:528:DC%2BC3cXjtlKms7c%3D 10.1073/pnas.0915174107 20160101
11. AJ Currie RG van der Most SA Broomfield, et al. 2008 Targeting the effector site with IFN-alphabeta-inducing TLR ligands reactivates tumor-resident CD8 T cell responses to eradicate established solid tumors J Immunol 180 1535 1544 1:CAS:528:DC%2BD1cXotlGltw%3D%3D 18209049
12. J Dannull Z Su D Rizzieri, et al. 2005 Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells J Clin Invest 115 3623 3633 1:CAS:528:DC%2BD2MXhtlSqtLjJ 10.1172/JCI25947 16308572 (Pubitemid 43121851)
13. M Del Vecchio E Bajetta S Canova, et al. 2007 Interleukin-12: biological properties and clinical application Clin Cancer Res 13 4677 4685 1:CAS:528:DC%2BD2sXptVGmsbY%3D 10.1158/1078-0432.CCR-07-0776 17699845 (Pubitemid 47294773)
14. M Dougan G Dranoff 2009 Immune therapy for cancer Annu Rev Immunol 27 83 117 1:CAS:528:DC%2BD1MXlsFSlsbo%3D 10.1146/annurev.immunol.021908.132544 19007331
15. G Dranoff 2004 Cytokines in cancer pathogenesis and cancer therapy Nat Rev Cancer 4 11 22 1:CAS:528:DC%2BD2cXos1Wjtg%3D%3D 10.1038/nrc1252 14708024 (Pubitemid 38111131)
16. GP Dunn LJ Old RD Schreiber 2004 The immunobiology of cancer immunosurveillance and immunoediting Immunity 21 137 148 1:CAS:528: DC%2BD2cXnsVKltrY%3D 10.1016/j.immuni.2004.07.017 15308095 (Pubitemid 39094044)
17. NK Egilmez YS Jong MS Sabel, et al. 2000 In situ tumor vaccination with interleukin-12-encapsulated biodegradable microspheres: induction of tumor regression and potent antitumor immunity Cancer Res 60 3832 3837 1:CAS:528:DC%2BD3cXlt1Gkt7Y%3D 10919657
18. NK Egilmez SD Hess F-A Chen, et al. 2002 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 62 2611 2617 1:CAS:528:DC%2BD38XjtlGrtrk%3D 11980657
19. NK Egilmez MO Kilinc T Gu, et al. 2007 Controlled-release particulate cytokine adjuvants for cancer therapy Endocr Metab Immune Disord Drug Targets 7 266 270 1:CAS:528:DC%2BD2sXhsVSgsbzK 10.2174/187153007782794335 18220947
20. M Epardaud KG Elpek MP Rubinstein, et al. 2008 Interleukin-15/ interleukin-15Ralpha complexes promote destruction of established tumors by reviving tumor-resident CD8+ T cells Cancer Res 68 2972 2983 1:CAS:528:DC%2BD1cXks1Ghsr0%3D 10.1158/0008-5472.CAN-08-0045 18413767 (Pubitemid 351556298)
21. G Forni M Giovarelli A Santoni 1985 Lymphokine-activated tumor inhibition in vivo. I. The local administration to interleukin 2 triggers nonreactive lymphocytes from tumor-bearing mice to inhibit tumor growth J Immunol 134 1305 1311 1:CAS:528:DyaL2MXpsVWntg%3D%3D 3871210
22. LM Francisco VH Salinas KE Brown, et al. 2009 PD-L1 regulates the development, maintenance, and function of induced regulatory T cells J Exp Med 206 3015 3029 1:CAS:528:DC%2BD1MXhs1WlsbrP 10.1084/jem.20090847 20008522
23. AB Frey N Monu 2006 Effector-phase tolerance: another mechanism of how cancer escapes antitumor immune response J Leukoc Biol 79 652 662 1:CAS:528:DC%2BD28XjsFCmur8%3D 10.1189/jlb.1105628 16415165 (Pubitemid 44835597)
24. AB Frey N Monu 2008 Signaling defects in anti-tumor T cells Immunol Rev 222 192 205 1:CAS:528:DC%2BD1cXlsFejt7w%3D 10.1111/j.1600-065X.2008.00606.x 18364003 (Pubitemid 351430368)
25. TF Gajewski 2007 Failure at the effector phase: immune barriers at the level of the melanoma tumor microenvironment Clin Cancer Res 13 5256 5261 1:CAS:528:DC%2BD2sXhtVCitL7J 10.1158/1078-0432.CCR-07-0892 17875753 (Pubitemid 47510348)
26. TF Gajewski Y Meng H Harlin 2006 Immune suppression in the tumor microenvironment J Immunother 29 233 240 1:CAS:528:DC%2BD28XksFKgsbg%3D 10.1097/01.cji.0000199193.29048.56 16699366 (Pubitemid 44297291)
27. T Gu MO Kilinc NK Egilmez 2008 Transient activation of tumor-associated T-effector/memory cells promotes eradication via NK-cell recruitment: minimal role for long-term T-cell immunity in cure of metastatic disease Cancer Immunol Immunother 57 997 1005 1:CAS:528:DC%2BD1cXltFeqtLo%3D 10.1007/s00262-007-0430-0 18049819
28. T Gu RB Rowswell-Turner MO Kilinc, et al. 2010 Central role of IFNgamma-indoleamine 2,3-dioxygenase axis in regulation of interleukin-12- mediated antitumor immunity Cancer Res 70 129 138 1:CAS:528:DC%2BC3cXkvFyi 10.1158/0008-5472.CAN-09-3170 20028855
29. K Higashi Y Inagaki K Fujimori, et al. 2003 Interferon-gamma interferes with transforming growth factor-β signaling through direct interaction of YB-1 with Smad3 J Biol Chem 278 43470 43479 1:CAS:528:DC%2BD3sXosFSrs7Y%3D 10.1074/jbc.M302339200 12917425 (Pubitemid 37345970)
30. HC Hill TF Conway Jr MS Sabel, et al. 2002 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 62 7254 7263 1:CAS:528:DC%2BD3sXhtVyqtQ%3D%3D 12499267
31. Y Huang N Obholzer R Fayad, et al. 2005 Turning on/off tumor-specific CTL response during progressive tumor growth J Immunol 175 3110 3116 1:CAS:528:DC%2BD2MXos1Giu7s%3D 16116200
32. CN Janicki SR Jenkinson NA Williams, et al. 2008 Loss of CTL function among high-avidity tumor-specific CD8+ T cells following tumor infiltration Cancer Res 68 2993 3000 1:CAS:528:DC%2BD1cXks1Ghsrs%3D 10.1158/0008-5472.CAN-07- 5008 18413769 (Pubitemid 351556300)
33. AG Jarnicki DR Fitzpatrick BW Robinson, et al. 1996 Altered CD3 chain and cytokine gene expression in tumor infiltrating T lymphocytes during the development of mesothelioma Cancer Lett 103 1 9 1:CAS:528:DyaK28XisFWhsbg%3D 10.1016/0304-3835(96)04178-X 8616801 (Pubitemid 26125158)
34. M Johansson DG Denardo LM Coussens 2008 Polarized immune responses differentially regulate cancer development Immunol Rev 222 145 154 1:CAS:528:DC%2BD1cXlsFejtrY%3D 10.1111/j.1600-065X.2008.00600.x 18363999 (Pubitemid 351430362)
35. MO Kilinc KS Aulakh RE Nair, et al. 2006 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 177 6962 6973 1:CAS:528:DC%2BD28XhtFGrtrrO 17082611
36. MO Kilinc T Gu J Harden, et al. 2009 Central role of tumor-associated CD8+ T effector/memory cells in restoring systemic antitumor immunity J Immunol 182 4217 4225 1:CAS:528:DC%2BD1MXjsVSjtbs%3D 10.4049/jimmunol.0802793 19299720
37. MO Kilinc RB Rowswell-Turner T Gu, et al. 2009 Activated CD8+ T-effector/memory cells eliminate CD4+ CD25+ Foxp3+ T-suppressor cells from tumors via FasL mediated apoptosis J Immunol 183 7656 7660 1:CAS:528: DC%2BD1MXhsFCkt73F 10.4049/jimmunol.0902625 19923444
38. CM Koebel W Vermi JB Swann, et al. 2007 Adaptive immunity maintains occult cancer in an equilibrium state Nature 450 903 907 1:CAS:528: DC%2BD2sXhtl2gsbjL 10.1038/nature06309 18026089 (Pubitemid 350231320)
39. M Koneru D Schaer N Monu, et al. 2005 Defective proximal TCR signaling inhibits CD8+ tumor-infiltrating lymphocyte lytic function J Immunol 174 1830 1840 1:CAS:528:DC%2BD2MXhtV2ku7Y%3D 15699109
40. MO Li YY Wan S Sanjabi, et al. 2006 Transforming growth factor-beta regulation of immune responses Annu Rev Immunol 24 99 146 1:CAS:528: DC%2BD28XkvFSqt7w%3D 10.1146/annurev.immunol.24.021605.090737 16551245
41. EY Lin JW Pollard 2004 Role of infiltrated leucocytes in tumour growth and spread Br J Cancer 90 2053 2058 1:STN:280:DC%2BD2czht1SqsQ%3D%3D 10.1038/sj.bjc.6601705 15164120 (Pubitemid 38869704)
42. A Mantovani P Romero AK Palucka, et al. 2008 Tumour immunity: effector response to tumour and role of the microenvironment Lancet 371 771 783 1:CAS:528:DC%2BD1cXislWitr0%3D 10.1016/S0140-6736(08)60241-X 18275997
43. H Mizoguchi JJ O'Shea DL Longo 1992 Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice Science 258 1795 1798 1:CAS:528:DyaK3sXlslOjsg%3D%3D 10.1126/science.1465616 1465616
44. V Monsurró E Wang Y Yamano, et al. 2004 Quiescent phenotype of tumor-specific CD8 + T cells following immunization Blood 104 1970 1978 10.1182/blood-2004-02-0525 15187028 (Pubitemid 39297845)
45. N Monu AB Frey 2007 Suppression of proximal T cell receptor signaling and lytic function in CD8 + tumor-infiltrating T cells Cancer Res 67 11447 11454 1:CAS:528:DC%2BD2sXhtlyiu7vN 10.1158/0008-5472.CAN-07-1441 18056473 (Pubitemid 350248573)
46. SN Mueller R Ahmed 2009 High antigen levels are the cause of T cell exhaustion during chronic viral infection Proc Natl Acad Sci USA 106 8623 8628 1:CAS:528:DC%2BD1MXnt1Sqs7Y%3D 10.1073/pnas.0809818106 19433785
47. S Nagaraj AG Schrum H-I Cho, et al. 2010 Mechanism of T cell tolerance induced by myeloid-derived suppressor cells J Immunol 184 3106 3116 1:CAS:528:DC%2BC3cXis1yitrs%3D 10.4049/jimmunol.0902661 20142361
48. RE Nair YS Jong SA Jones, et al. 2006 IL-12+ GM-CSF microsphere therapy induces eradication of advanced spontaneous tumors in her-2/neu transgenic mice but fails to achieve long-term cure due to the inability to maintain effector T-cell activity J Immunother 29 10 20 1:CAS:528:DC%2BD2MXhtlagt7nO 10.1097/01.cji.0000175489.19314.d2 16365596
49. RE Nair MO Kilinc SA Jones, et al. 2006 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 176 7325 7334 1:CAS:528: DC%2BD28Xlt1Clurg%3D 16751376
50. DA Oble R Loewe P Yu, et al. 2009 Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in human melanoma Cancer Immun 9 3 22 19338264
51. I-K Park LD Shultz JJ Letterio, et al. 2005 TGF-β1 inhibits T-bet induction by IFN-gamma in murine CD4+ T cells through the protein tyrosine phosphatase Src homology region 2 domain-containing phosphatase-1 J Immunol 175 5666 5674 1:CAS:528:DC%2BD2MXhtFahurrJ 16237056
52. RV Parry JM Chemnitz KA Frauwirth, et al. 2005 CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms Mol Cell Biol 25 9543 9553 1:CAS:528:DC%2BD2MXhtFOns77N 10.1128/MCB.25.21.9543-9553.2005 16227604 (Pubitemid 41507854)
53. KS Peggs SA Quezada JP Allison 2008 Cell intrinsic mechanisms of T-cell inhibition and application to cancer therapy Immunol Rev 224 141 165 1:CAS:528:DC%2BD1cXhtF2qurnL 10.1111/j.1600-065X.2008.00649.x 18759925
54. S Radoja M Saio D Schaer, et al. 2001 CD8+ tumor-infiltrating T cells are deficient in perforin-mediated cytolytic activity due to defective microtubule-organizing center mobilization and lytic granule exocytosis J Immunol 167 5042 5051 1:CAS:528:DC%2BD3MXotVWjsrg%3D 11673513
55. AH Rook GS Wood EK Yoo, et al. 1999 Interleukin-12 therapy of cutaneous T-cell lymphoma induces lesion regression and cytotoxic T-cell responses Blood 94 902 908 1:CAS:528:DyaK1MXkvFCjurg%3D 10419880
56. SA Rosenberg ME Dudley 2009 Adoptive cell therapy for the treatment of patients with metastatic melanoma Curr Opin Immunol 21 233 240 1:CAS:528:DC%2BD1MXlsVCgtb8%3D 10.1016/j.coi.2009.03.002 19304471
57. SA Rosenberg RM Sherry KE Morton, et al. 2005 Tumor progression can occur despite the induction of very high levels of self/tumor antigen-specific CD8+ T cells in patients with melanoma J Immunol 175 6169 6176 1:CAS:528: DC%2BD2MXhtFahu77P 16237114
58. EM Shevach 2009 Mechanisms of Foxp3+ T regulatory cell-mediated suppression Immunity 30 636 645 1:CAS:528:DC%2BD1MXosVCks7g%3D 10.1016/j.immuni.2009.04.010 19464986
59. M Simpson-Abelson RB Bankert 2008 Targeting the TCR signaling checkpoint: a therapeutic strategy to reactivate memory T cells in the tumor microenvironment Expert Opin Ther Targets 12 477 490 1:CAS:528: DC%2BD1cXjtlGlu7o%3D 10.1517/14728222.12.4.477 18348683 (Pubitemid 351546372)
60. Y Sugiyama M Kato F-A Chen, et al. 2001 Human inflammatory cells within the tumor microenvironment of lung tumor xenografts mediate tumor growth suppression in situ that depends on and is augmented by interleukin-12 J Immunother 24 37 45 1:CAS:528:DC%2BD3MXps1ajsg%3D%3D 10.1097/00002371-200101000- 00005 11211147 (Pubitemid 32101966)
61. JE Talmadge M Donkor E Scholar 2007 Inflammatory cell infiltration of tumors: Jekyll or Hyde Cancer Metastasis Rev 26 373 400 10.1007/s10555-007-9072- 0 17717638 (Pubitemid 350115102)
62. DA Thomas J Massagué 2005 TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance Cancer Cell 8 369 380 1:CAS:528:DC%2BD2MXht12gsbvK 10.1016/j.ccr.2005.10.012 16286245 (Pubitemid 41579832)
63. G Trinchieri 2003 Interleukin-12 and the regulation of innate resistance and adaptive immunity Nat Rev Immunol 3 133 146 1:CAS:528:DC%2BD3sXot12gug%3D%3D 10.1038/nri1001 12563297 (Pubitemid 37328691)
64. K Tsung JP Dolan YL Tsung, et al. 2002 Macrophages as effector cells in interleukin 12-induced T cell-dependent tumor rejection Cancer Res 62 5069 5075 1:CAS:528:DC%2BD38Xmslyks70%3D 12208763
65. L Ulloa J Doody J Massagué 1999 Inhibition of transforming growth factor-beta/SMAD signaling by the interferon-gamma/STAT pathway Nature 397 710 713 1:CAS:528:DyaK1MXhs1ekurc%3D 10.1038/17826 10067896 (Pubitemid 29108392)
66. RG Uzzo P Rayman V Kolenko, et al. 1999 Renal cell carcinoma-derived gangliosides suppress nuclear factor-kappaB activation in T cells J Clin Invest 104 769 776 1:CAS:528:DyaK1MXmtFGltbo%3D 10.1172/JCI6775 10491412
67. WS Webster RH Thompson KJ Harris, et al. 2007 Targeting molecular and cellular inhibitory mechanisms for improvement of antitumor memory responses reactivated by tumor cell vaccine J Immunol 179 2860 2869 1:CAS:528: DC%2BD2sXpt1Sms7o%3D 17709500
68. TL Whiteside 2004 Down-regulation of zeta-chain expression in T cells: a biomarker of prognosis in cancer? Cancer Immunol Immunother 53 865 878 1:CAS:528:DC%2BD2cXntV2hsLs%3D 15118842
69. TL Whiteside 2008 The tumor microenvironment and its role in promoting tumor growth Oncogene 27 5904 5912 1:CAS:528:DC%2BD1cXhtF2msbbK 10.1038/onc.2008.271 18836471
70. P Yu Y Lee W Liu, et al. 2005 Intratumor depletion of CD4+ cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors J Exp Med 201 779 791 1:CAS:528:DC%2BD2MXitl2rt7s%3D 10.1084/jem.20041684 15753211 (Pubitemid 40395122)
71. J Yu M Wei B Becknell, et al. 2006 Pro- and antiinflammatory cytokine signaling: reciprocal antagonism regulates interferon-gamma production by human natural killer cells Immunity 24 575 590 1:CAS:528:DC%2BD28XlsFWqt74%3D 10.1016/j.immuni.2006.03.016 16713975 (Pubitemid 43728149)
72. X Zang JP Allison 2007 The B7 family and cancer therapy: costimulation and coinhibition Clin Cancer Res 13 5271 5279 1:CAS:528:DC%2BD2sXhtVCitL7L 10.1158/1078-0432.CCR-07-1030 17875755 (Pubitemid 47510350)