PD-1/SHP-2 inhibits Tc1/Th1 phenotypic responses and the activation of t cells in the tumor microenvironment

Cancer Research

Volumn 75, Issue 3, 2015, Pages 508-518

  Li, Jing ^a   Jie, Hyun Bae ^b   Lei, Yu ^b   Gildener Leapman, Neil ^b   Trivedi, Sumita ^b   Green, Tony ^c   Kane, Lawrence P ^b   Ferris, Robert L ^b,d  

^a Tsinghua University ^*  (China)

^b UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF PITTSBURGH   (United States)

^d UNIVERSITY OF PITTSBURGH CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GAMMA INTERFERON; INTERLEUKIN 10; INTERLEUKIN 2; INTERLEUKIN 4; INTERLEUKIN 5; PROGRAMMED DEATH 1 RECEPTOR; PROTEIN S6; PROTEIN TYROSINE PHOSPHATASE SHP 2; STAT1 PROTEIN; STAT4 PROTEIN; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR T BET; TUMOR NECROSIS FACTOR ALPHA; CYTOKINE; IMMUNOSUPPRESSIVE AGENT; LIGAND; PDCD1 PROTEIN, HUMAN; PTPN11 PROTEIN, HUMAN;

ADULT; AGED; ARTICLE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELLULAR IMMUNITY; CLINICAL ARTICLE; CONTROLLED STUDY; CORRELATIONAL STUDY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DOWN REGULATION; FEMALE; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HUMAN; HUMAN CELL; HUMAN TISSUE; INTRACELLULAR SIGNALING; LYMPHOCYTE DIFFERENTIATION; MALE; MIDDLE AGED; PERIPHERAL LYMPHOCYTE; PHENOTYPE; PROTEIN EXPRESSION; PROTEIN FUNCTION; T LYMPHOCYTE ACTIVATION; TH1 CELL; TH2 CELL; TUMOR ASSOCIATED LEUKOCYTE; TUMOR MICROENVIRONMENT; UPREGULATION; CARCINOMA, SQUAMOUS CELL; CYTOLOGY; HEAD AND NECK NEOPLASMS; IMMUNOLOGY; IMMUNOTHERAPY; LYMPHOCYTE; METABOLISM; NEOPLASM; PROCEDURES; PROSPECTIVE STUDY;

ADULT; AGED; CARCINOMA, SQUAMOUS CELL; CD4-POSITIVE T-LYMPHOCYTES; CYTOKINES; FEMALE; HEAD AND NECK NEOPLASMS; HUMANS; IMMUNOSUPPRESSIVE AGENTS; IMMUNOTHERAPY; LIGANDS; LYMPHOCYTES; LYMPHOCYTES, TUMOR-INFILTRATING; MALE; MIDDLE AGED; NEOPLASMS; PROGRAMMED CELL DEATH 1 RECEPTOR; PROSPECTIVE STUDIES; PROTEIN TYROSINE PHOSPHATASE, NON-RECEPTOR TYPE 11; TH1 CELLS; TUMOR MICROENVIRONMENT;

EID: 84961289417     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-14-1215     Document Type: Article

References (35)

1. Tong CC, Kao J, Sikora AG. Recognizing and reversing the immunosuppressive tumor microenvironment of head and neck cancer. Immunol Res 2012;54:266-74.
2. Jie HB, Gildener-Leapman N, Li J, Srivastava RM, Gibson SP, Whiteside TL, et al. Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients. Br J Cancer 2013;109:2629-35.
3. Salvi S, Fontana V, Boccardo S, Merlo DF, Margallo E, Laurent S, et al. Evaluation of CTLA-4 expression and relevance as a novel prognostic factor in patients with non-small cell lung cancer. Cancer Immunol Immun 2012;61:1463-72.
4. Lyford-Pike S, Peng S, Young GD, Taube JM, Westra WH, Akpeng B, et al. Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma. Cancer Res 2013;73:1733-41.
5. Fourcade J, Sun Z, Pagliano O, Guillaume P, Luescher IF, Sander C, et al. CD8(+) T cells specific for tumor antigens can be rendered dysfunctional by the tumor microenvironment through upregulation of the inhibitory receptors BTLA and PD-1. Cancer Res 2012;72:887-96.
6. Woo SR, Turnis ME, Goldberg MV, Bankoti J, Selby M, Nirschl CJ, et al. Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate Tcell function to promote tumoral immune escape. Cancer Res 2012;72:917-27.
7. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012;12:252-64.
8. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survivalwith ipilimumab in patients with metastatic melanoma. N Engl J Med 2010;363:711-23.
9. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012;366:2443-54.
10. Yang Y, Ochando JC, Bromberg JS, Ding Y. Identification of a distant T-bet enhancer responsive to IL-12/Stat4 and IFNgamma/Stat1 signals. Blood 2007;110:2494-500.
11. Thieu VT, Yu Q, Chang HC, Yeh N, Nguyen ET, Sehra S, et al. Signal transducer and activator of transcription 4 is required for the transcription factor T-bet to promote T helper 1 cell-fate determination. Immunity 2008;29:679-90.
12. Wei L, Vahedi G, Sun HW, Watford WT, Takatori H, Ramos HL, et al. Discrete roles of STAT4 and STAT6 transcription factors in tuning epigenetic modifications and transcription during T helper cell differentiation. Immunity 2010;32:840-51.
13. Nomi T, Sho M, Akahori T, Hamada K, Kubo A, Kanehiro H, et al. Clinical significance and therapeutic potential of the programmed death-1 ligand/programmed death-1 pathway in human pancreatic cancer. Clin Cancer Res 2007;13:2151-7.
14. Badoual C, Hans S, Merillon N, Van Ryswick C, Ravel P, Benhamouda N, et al. PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-associated head and neck cancer. Cancer Res 2013;73:128-38.
15. Leibowitz MS, Srivastava RM, Andrade Filho PA, Egloff AM, Wang L, Seethala RR, et al. SHP2 is overexpressed and inhibits pSTAT1-mediated APM component expression, T-cell attracting chemokine secretion, and CTL recognition in head and neck cancer cells. Clin Cancer Res 2013;19:798-808.
16. Wu X, Guo W, Wu L, Gu Y, Gu L, Xu S, et al. Selective sequestration of STAT1 in the cytoplasm via phosphorylated SHP-2 ameliorates murine experimental colitis. J Immunol 2012;189:3497-507.
17. Hoff H, Brunner-Weinzierl MC. The tyrosine phosphatase SHP-2 regulates differentiation and apoptosis of individual primary T lymphocytes. Eur J Immunol 2007;37:1072-86.
18. Yamamoto R, Nishikori M, Kitawaki T, Sakai T, Hishizawa M, Tashima M, et al. PD-1-PD-1 ligand interaction contributes to immunosuppressive microenvironment of Hodgkin lymphoma. Blood 2008;111:3220-4.
19. Sulic S, Panic L, Barkic M, Mercep M, Uzelac M, Volarevic S. Inactivation of S6 ribosomal protein gene in T lymphocytes activates a p53-dependent checkpoint response. Genes Dev 2005;19:3070-82.
20. Francisco LM, Salinas VH, Brown KE, Vanguri VK, Freeman GJ, Kuchroo VK, et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med 2009;206:3015-29.
21. Lee J, Su EW, Zhu C, Hainline S, Phuah J, Moroco JA, et al. Phosphotyrosine-dependent coupling of Tim-3 to T-cell receptor signaling pathways. Mol Cell Biol 2011;31:3963-74.
22. Chemnitz JM, Parry RV, Nichols KE, June CH, Riley JL. 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;173:945-54.
23. + T lymphocytes infiltrating human tumors. PLoS ONE 2011;6:e17621.
24. Yokosuka T, Takamatsu M, Kobayashi-Imanishi W, Hashimoto-Tane A, AzumaM, Saito T. Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2. J Exp Med 2012;209:1201-17.
25. Shu RG, Wang FW, Yang YM, Liu YX, Tan RX. Antibacterial and xanthine oxidase inhibitory cerebrosides from Fusariumsp. IFB-121, an endophytic fungus in Quercus variabilis. Lipids 2004;39:667-73.
26. Ferris RL, Whiteside TL, Ferrone S. Immune escape associated with functional defects in antigen-processing machinery in head and neck cancer. Clin Cancer Res 2006;12:3890-5.
27. Lopez-Albaitero A, Nayak JV, Ogino T, Machandia A, Gooding W, DeLeo AB, et al. Role of antigen-processing machinery in the in vitro resistance of squamous cell carcinoma of the head and neck cells to recognition by CTL. J Immunol 2006;176:3402-9.
28. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science 2011;331:1565-70.
29. + T cells in the circulation of patients with squamous cell carcinoma of the head and neck. Clin Cancer Res 2007;13:6301-11.
30. + regulatory T cells. J Immunol 2006;177:896-904.
31. Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol 2012;12:253-68.
32. Ikeda H, Chamoto K, Tsuji T, Suzuki Y, Wakita D, Takeshima T, et al. The critical role of type-1 innate and acquired immunity in tumor immunotherapy. Cancer Sci 2004;95:697-703.
33. Dobrzanski MJ, Reome JB, Hylind JC, Rewers-Felkins KA. CD8-mediated type 1 antitumor responses selectively modulate endogenous differentiated and nondifferentiated T cell localization, activation, and function in progressive breast cancer. J Immunol 2006;177:8191-201.
34. Dulos J, Carven GJ, van Boxtel SJ, Evers S, Driessen-Engels LJ, Hobo W, et al. PD-1 blockade augments Th1 and Th17 and suppresses Th2 responses in peripheral blood from patients with prostate and advanced melanoma cancer. J Immunother 2012;35:169-78.
35. Duraiswamy J, Kaluza KM, Freeman GJ, Coukos G. Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors. Cancer Res 2013;73:3591-603.