High DGK-α and disabled MAPK pathways cause dysfunction of human tumor-infiltrating CD8 + T cells that is reversible by pharmacologic intervention

Journal of Immunology

Volumn 188, Issue 12, 2012, Pages 5990-6000

  Prinz, Petra U ^a   Mendler, Anna N ^a   Masouris, Ilias ^a   Durner, Leopold ^b   Oberneder, Ralph ^b   Noessner, Elfriede ^a  

^a INSTITUTE OF EPIDEMIOLOGY   (Germany)

^b Urology Clinic Munich Planegg   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIN DEPENDENT KINASE INHIBITOR 1B; CYCLIN E; DIACYLGLYCEROL KINASE; DIACYLGLYCEROL KINASE ALPHA; GAMMA INTERFERON; GLYCOGEN SYNTHASE KINASE 3; I KAPPA B; INTERLEUKIN 2; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHOLIPASE C GAMMA; PROTEIN KINASE B; PROTEIN TYROSINE KINASE; STRESS ACTIVATED PROTEIN KINASE; T LYMPHOCYTE RECEPTOR; UNCLASSIFIED DRUG;

ADULT; AGED; ARTICLE; CD8+ T LYMPHOCYTE; CD8+ TUMOR INFILTRATING T LYMPHOCYTE; CELL CYCLE G1 PHASE; CELL CYCLE S PHASE; CLINICAL ARTICLE; CONTROLLED STUDY; CYTOKINE PRODUCTION; DEGRANULATION; ENZYME ANALYSIS; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; EXOCYTOSIS; FEMALE; HUMAN; HUMAN CELL; HUMAN TISSUE; KIDNEY CARCINOMA; MALE; PRIORITY JOURNAL; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; STEADY STATE;

ADULT; AGED; AGED, 80 AND OVER; CARCINOMA, RENAL CELL; CD8-POSITIVE T-LYMPHOCYTES; DIACYLGLYCEROL KINASE; ENZYME INHIBITORS; EXOCYTOSIS; FEMALE; FLOW CYTOMETRY; FLUORESCENT ANTIBODY TECHNIQUE; HUMANS; INTERLEUKIN-2; KIDNEY NEOPLASMS; LYMPHOCYTE ACTIVATION; LYMPHOCYTES, TUMOR-INFILTRATING; MALE; MAP KINASE SIGNALING SYSTEM; MICROSCOPY, CONFOCAL; MIDDLE AGED; NEOPLASM STAGING; SIGNAL TRANSDUCTION;

EID: 84862611102     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1103028     Document Type: Article

References (51)

1. Geiger, C., E. Nössner, B. Frankenberger, C. S. Falk, H. Pohla, and D. J. Schendel. 2009. Harnessing innate and adaptive immunity for adoptive cell therapy of renal cell carcinoma. J. Mol. Med. 87: 595-612.
2. Vogelzang, N. J., and W. M. Stadler. 1998. Kidney cancer. Lancet 352: 1691-1696. (Pubitemid 28526138)
3. Reeves, D. J., and C. Y. Liu. 2009. Treatment of metastatic renal cell carcinoma. Cancer Chemother. Pharmacol. 64: 11-25.
4. Finke, J. H., P. Rayman, J. Alexander, M. Edinger, R. R. Tubbs, R. Connelly, E. Pontes, and R. Bukowski. 1990. Characterization of the cytolytic activity of CD4+ and CD8+ tumor-infiltrating lymphocytes in human renal cell carcinoma. Cancer Res. 50: 2363-2370. (Pubitemid 20134496)
5. Schendel, D. J., R. Oberneder, C. S. Falk, P. Jantzer, S. Kressenstein, B. Maget, A. Hofstetter, G. Riethmüller, and E. Nössner. 1997. Cellular and molecular analyses of major histocompatibility complex (MHC) restricted and non-MHC-restricted effector cells recognizing renal cell carcinomas: problems and perspectives for immunotherapy. J. Mol. Med. 75: 400-413. (Pubitemid 27297010)
6. Jantzer, P., and D. J. Schendel. 1998. Human renal cell carcinoma antigenspecific CTLs: antigen-driven selection and long-term persistence in vivo. Cancer Res. 58: 3078-3086. (Pubitemid 28335090)
7. Leisegang, M., A. Turqueti-Neves, B. Engels, T. Blankenstein, D. J. Schendel, W. Uckert, and E. Noessner. 2010. T-cell receptor gene-modified T cells with shared renal cell carcinoma specificity for adoptive T-cell therapy. Clin. Cancer Res. 16: 2333-2343.
8. Gajewski, T. F., Y. Meng, C. Blank, I. Brown, A. Kacha, J. Kline, and H. Harlin. 2006. Immune resistance orchestrated by the tumor microenvironment. Immunol. Rev. 213: 131-145. (Pubitemid 44401498)
9. Frankenberger, B., E. Noessner, and D. J. Schendel. 2007. Immune suppression in renal cell carcinoma. Semin. Cancer Biol. 17: 330-343. (Pubitemid 47211966)
10. Mantovani, A., P. Romero, A. K. Palucka, and F. M. Marincola. 2008. Tumour immunity: effector response to tumour and role of the microenvironment. Lancet 371: 771-783.
11. Schleypen, J. S., N. Baur, R. Kammerer, P. J. Nelson, K. Rohrmann, E. F. Gröne, M. Hohenfellner, A. Haferkamp, H. Pohla, D. J. Schendel, et al. 2006. Cytotoxic markers and frequency predict functional capacity of natural killer cells infiltrating renal cell carcinoma. Clin. Cancer Res. 12: 718-725. (Pubitemid 43259850)
12. Figel, A. M., D. Brech, P. U. Prinz, U. K. Lettenmeyer, J. Eckl, A. Turqueti- Neves, J. Mysliwietz, D. Anz, N. Rieth, N. Muenchmeier, et al. 2011. Human renal cell carcinoma induces a dendritic cell subset that uses T-cell crosstalk for tumor-permissive milieu alterations. Am. J. Pathol. 179: 436-451.
13. Dengjel, J., M. D. Nastke, C. Gouttefangeas, G. Gitsioudis, O. Schoor, F. Altenberend, M. Müller, B. Krämer, A. Missiou, M. Sauter, et al. 2006. Unexpected abundance of HLA class II presented peptides in primary renal cell carcinomas. Clin. Cancer Res. 12: 4163-4170.
14. Sáenz-López, P., C. Gouttefangeas, J. Hennenlotter, A. Concha, I. Maleno, F. Ruiz-Cabello, J. M. Cózar, M. Tallada, A. Stenzl, H. G. Rammensee, et al. 2010. Higher HLA class I expression in renal cell carcinoma than in autologous normal tissue. Tissue Antigens 75: 110-118.
15. Van den Hove, L. E., S. W. Van Gool, H. Van Poppel, L. Baert, L. Coorevits, B. Van Damme, and J. L. Ceuppens. 1997. Phenotype, cytokine production and cytolytic capacity of fresh (uncultured) tumour-infiltrating T lymphocytes in human renal cell carcinoma. Clin. Exp. Immunol. 109: 501-509. (Pubitemid 27402320)
16. Radoja, S., and A. B. Frey. 2000. Cancer-induced defective cytotoxic T lymphocyte effector function: another mechanism how antigenic tumors escape immune-mediated killing. Mol. Med. 6: 465-479.
17. Janicki, C. N., S. R. Jenkinson, N. A. Williams, and D. J. Morgan. 2008. Loss of CTL function among high-avidity tumor-specific CD8+ T cells following tumor infiltration. Cancer Res. 68: 2993-3000. (Pubitemid 351556300)
18. Imai, N., H. Ikeda, I. Tawara, and H. Shiku. 2009. Tumor progression inhibits the induction of multifunctionality in adoptively transferred tumor-specific CD8+ T cells. Eur. J. Immunol. 39: 241-253.
19. Vazquez-Cintron, E. J., N. R. Monu, and A. B. Frey. 2010. Tumor-induced disruption of proximal TCR-mediated signal transduction in tumor-infiltrating CD8 + lymphocytes inactivates antitumor effector phase. J. Immunol. 185: 7133-7140.
20. Huse, M. 2009. The T-cell-receptor signaling network. J. Cell Sci. 122: 1269-1273.
21. Robertson, L. K., L. R. Mireau, and H. L. Ostergaard. 2005. A role for phosphatidylinositol 3-kinase in TCR-stimulated ERK activation leading to paxillin phosphorylation and CTL degranulation. J. Immunol. 175: 8138-8145. (Pubitemid 41798377)
22. Radoja, S., A. B. Frey, and S. Vukmanovic. 2006. T-cell receptor signaling events triggering granule exocytosis. Crit. Rev. Immunol. 26: 265-290. (Pubitemid 44079774)
23. Manning, B. D., and L. C. Cantley. 2007. AKT/PKB signaling: navigating downstream. Cell 129: 1261-1274. (Pubitemid 46962095)
24. Rieber, E. P. 1989. T-cell section report. In Leucocyte Typing Vol. IV: White Cell Differentiation Antigens. W. Knapp, ed. Oxford University Press, Oxford, p. 229.
25. Baudin, E., C. Do Cao, A. F. Cailleux, S. Leboulleux, J. P. Travagli, and M. Schlumberger. 2003. Positive predictive value of serum thyroglobulin levels, measured during the first year of follow-up after thyroid hormone withdrawal, in thyroid cancer patients. J. Clin. Endocrinol. Metab. 88: 1107-1111. (Pubitemid 36337763)
26. Medley, Q. G., N. Kedersha, S. O'Brien, Q. Tian, S. F. Schlossman, M. Streuli, and P. Anderson. 1996. Characterization of GMP-17, a granule membrane protein that moves to the plasma membrane of natural killer cells following target cell recognition. Proc. Natl. Acad. Sci. USA 93: 685-689. (Pubitemid 26048553)
27. Felgar, R. E., K. E. Salhany, W. R. Macon, G. G. Pietra, and M. C. Kinney. 1999. The expression of TIA-1+ cytolytic-type granules and other cytolytic lymphocyte-associated markers in CD30+ anaplastic large cell lymphomas (ALCL): correlation with morphology, immunophenotype, ultrastructure, and clinical features. Hum. Pathol. 30: 228-236. (Pubitemid 29086957)
28. Betts, M. R., J. M. Brenchley, D. A. Price, S. C. De Rosa, D. C. Douek, M. Roederer, and R. A. Koup. 2003. Sensitive and viable identification of antigen-specific CD8+ T cells by a flow cytometric assay for degranulation. J. Immunol. Methods 281: 65-78. (Pubitemid 37324571)
29. Beyer, M., J. Karbach, M. R. Mallmann, T. Zander, D. Eggle, S. Classen, S. Debey-Pascher, M. Famulok, E. Jäger, and J. L. Schultze. 2009. Cancer vaccine enhanced, non-tumor-reactive CD8(+) T cells exhibit a distinct molecular program associated with "division arrest anergy". Cancer Res. 69: 4346-4354.
30. Singh, K., P. Deshpande, S. Pryshchep, I. Colmegna, V. Liarski, C. M. Weyand, and J. J. Goronzy. 2009. ERK-dependent T cell receptor threshold calibration in rheumatoid arthritis. J. Immunol. 183: 8258-8267.
31. Wang, E., A. Worschech, and F. M. Marincola. 2008. The immunologic constant of rejection. Trends Immunol. 29: 256-262.
32. Swann, J. B., and M. J. Smyth. 2007. Immune surveillance of tumors. J. Clin. Invest. 117: 1137-1146. (Pubitemid 46718398)
33. Voskoboinik, I., M. A. Dunstone, K. Baran, J. C. Whisstock, and J. A. Trapani. 2010. Perforin: structure, function, and role in human immunopathology. Immunol. Rev. 235: 35-54.
34. Saibil, S. D., E. K. Deenick, and P. S. Ohashi. 2007. The sound of silence: modulating anergy in T lymphocytes. Curr. Opin. Immunol. 19: 658-664. (Pubitemid 350236809)
35. Zheng, Y., Y. Zha, and T. F. Gajewski. 2008. Molecular regulation of T-cell anergy. EMBO Rep. 9: 50-55.
36. Macián, F., F. García-Cózar, S. H. Im, H. F. Horton, M. C. Byrne, and A. Rao. 2002. Transcriptional mechanisms underlying lymphocyte tolerance. Cell 109: 719-731. (Pubitemid 34722268)
37. Baine, I., B. T. Abe, and F. Macian. 2009. Regulation of T-cell tolerance by calcium/NFAT signaling. Immunol. Rev. 231: 225-240.
38. Wherry, E. J., S. J. Ha, S. M. Kaech, W. N. Haining, S. Sarkar, V. Kalia, S. Subramaniam, J. N. Blattman, D. L. Barber, and R. Ahmed. 2007. Molecular signature of CD8+ T cell exhaustion during chronic viral infection. Immunity 27: 670-684. (Pubitemid 47615511)
39. Quigley, M., F. Pereyra, B. Nilsson, F. Porichis, C. Fonseca, Q. Eichbaum, B. Julg, J. L. Jesneck, K. Brosnahan, S. Imam, et al. 2010. Transcriptional analysis of HIV-specific CD8+ T cells shows that PD-1 inhibits T cell function by upregulating BATF. Nat. Med. 16: 1147-1151.
40. Kim, P. S., and R. Ahmed. 2010. Features of responding T cells in cancer and chronic infection. Curr. Opin. Immunol. 22: 223-230.
41. Zhong, X. P., R. Guo, H. Zhou, C. Liu, and C. K. Wan. 2008. Diacylglycerol kinases in immune cell function and self-tolerance. Immunol. Rev. 224: 249-264.
42. Quann, E. J., E. Merino, T. Furuta, and M. Huse. 2009. Localized diacylglycerol drives the polarization of the microtubule-organizing center in T cells. Nat. Immunol. 10: 627-635.
43. Gorentla, B. K., C. K. Wan, and X. P. Zhong. 2011. Negative regulation of mTOR activation by diacylglycerol kinases. Blood 117: 4022-4031.
44. Surjit, M., and S. K. Lal. 2007. Glycogen synthase kinase-3 phosphorylates and regulates the stability of p27kip1 protein. Cell Cycle 6: 580-588. (Pubitemid 46440432)
45. Duré, M., and F. Macian. 2009. IL-2 signaling prevents T cell anergy by inhibiting the expression of anergy-inducing genes. Mol. Immunol. 46: 999-1006.
46. Luo, B., D. S. Regier, S. M. Prescott, and M. K. Topham. 2004. Diacylglycerol kinases. Cell. Signal. 16: 983-989. (Pubitemid 38798049)
47. Attig, S., J. Hennenlotter, G. Pawelec, G. Klein, S. D. Koch, H. Pircher, S. Feyerabend, D. Wernet, A. Stenzl, H. G. Rammensee, and C. Gouttefangeas. 2009. Simultaneous infiltration of polyfunctional effector and suppressor T cells into renal cell carcinomas. Cancer Res. 69: 8412-8419.
48. Radoja, S., M. Saio, D. Schaer, M. Koneru, S. Vukmanovic, and A. B. Frey. 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. (Pubitemid 33009737)
49. Dubinett, S. M., L. Patrone, J. Tobias, A. J. Cochran, D. R. Wen, and W. H. McBride. 1993. Intratumoral interleukin-2 immunotherapy: activation of tumor-infiltrating and splenic lymphocytes in vivo. Cancer Immunol. Immunother. 36: 156-162. (Pubitemid 23047713)
50. -/-) mice depends on conditioned T cells. Cancer Immunol. Immunother. 55: 861-866.
51. Riese, M. J., J. Grewal, J. Das, T. Zou, V. Patil, A. K. Chakraborty, and G. A. Koretzky. 2011. Decreased diacylglycerol metabolism enhances ERK activation and augments CD8+ T cell functional responses. J. Biol. Chem. 286: 5254-5265.