STAT3 signaling is required for optimal regression of large established tumors in mice treated with anti-OX40 and TGFβ Receptor Blockade

Cancer Immunology Research

Volumn 3, Issue 5, 2015, Pages 526-535

  Triplett, Todd A ^a,b   Tucker, Christopher G ^a   Triplett, Kendra C ^a   Alderman, Zefora ^a   Sun, Lihong ^c   Ling, Leona E ^c   Akporiaye, Emmanuel T ^a,b   Weinberg, Andrew D ^a,b  

^a EARLE A CHILES RESEARCH INSTITUTE   (United States)

^b OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^c BIOGEN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTI OX40; ANTINEOPLASTIC AGENT; GAMMA INTERFERON; GRANZYME B; RECEPTOR BLOCKING AGENT; STAT3 PROTEIN; TRANSFORMING GROWTH FACTOR BETA RECEPTOR INHIBITOR; UNCLASSIFIED DRUG; AZABICYCLO DERIVATIVE; CD134 ANTIGEN; MONOCLONAL ANTIBODY; SM16 COMPOUND; STAT3 PROTEIN, MOUSE; TRANSFORMING GROWTH FACTOR BETA RECEPTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER IMMUNOTHERAPY; CANCER SURVIVAL; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL INFILTRATION; CELL ISOLATION; CELL PROLIFERATION; COMPARATIVE STUDY; CONTROLLED STUDY; DRUG POTENCY; FEMALE; FLOW CYTOMETRY; IMMUNOCOMPETENT CELL; IMMUNOSUPPRESSIVE TREATMENT; IN VITRO STUDY; LARGE ESTABLISHED TUMOR; LEWIS LUNG CARCINOMA CELL; MOUSE; NEOPLASM; NONHUMAN; OVERALL SURVIVAL; PHENOTYPE; PROMOTER REGION; SARCOMA CELL; SIGNAL TRANSDUCTION; TUMOR GROWTH; TUMOR MICROENVIRONMENT; TUMOR MODEL; TUMOR REGRESSION; ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; IMMUNOLOGY; METABOLISM; NEOPLASMS; PATHOLOGY; TRANSGENIC MOUSE; TUMOR CELL LINE;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; AZABICYCLO COMPOUNDS; CELL LINE, TUMOR; FEMALE; MICE, INBRED C57BL; MICE, TRANSGENIC; NEOPLASMS; RECEPTORS, OX40; RECEPTORS, TRANSFORMING GROWTH FACTOR BETA; SIGNAL TRANSDUCTION; STAT3 TRANSCRIPTION FACTOR;

EID: 84962319761     PISSN: 23266066     EISSN: 23266074     Source Type: Journal    
DOI: 10.1158/2326-6066.CIR-14-0187     Document Type: Article

References (48)

1. Fujita T, Ukyo N, Hori T, Uchiyama T. Functional characterization of OX40 expressed on human CD8+ T cells. Immunol Lett 2006;106:27-33.
2. Gramaglia I, Weinberg AD, Lemon M, Croft M. Ox-40 ligand: a potent costimulatory molecule for sustaining primary CD4 T cell responses. J Immunol 1998;161:6510-7.
3. Weinberg AD, Rivera MM, Prell R, Morris A, Ramstad T, Vetto JT, et al. Engagement of the OX-40 receptor in vivo enhances antitumor immunity. J Immunol 2000;164:2160-9.
4. Croft M. Control of immunity by the TNFR-related molecule OX40 (CD134). Annu Rev Immunol 2010;28:57-78.
5. Redmond WL, Ruby CE, Weinberg AD. The role of OX40-mediated costimulation in T-cell activation and survival. Crit Rev Immunol 2009;29: 187-201.
6. Curti BD, Kovacsovics-Bankowski M, Morris N, Walker E, Chisholm L, Floyd K, et al. OX40 is a potent immune-stimulating target in late-stage cancer patients. Cancer Res 2013;73:7189-98.
7. Morris A, Vetto JT, Ramstad T, Funatake CJ, Choolun E, Entwisle C, et al. Induction of anti-mammary cancer immunity by engaging the OX-40 receptor in vivo. Breast Cancer Res Treat 2001;67:71-80.
8. Song A, Song J, Tang X, Croft M. Cooperation between CD4 and CD8 T cells for anti-tumor activity is enhanced by OX40 signals. Eur J Immunol 2007; 37:1224-32.
9. Gough MJ, Crittenden MR, Sarff M, Pang P, Seung SK, Vetto JT, et al. Adjuvant therapy with agonistic antibodies to CD134 (OX40) increases local control after surgical or radiation therapy of cancer in mice. J Immunother 2010;33:798-809.
10. Gough MJ, Ruby CE, Redmond WL, Dhungel B, Brown A, Weinberg AD. OX40 agonist therapy enhances CD8 infiltration and decreases immune suppression in the tumor. Cancer Res 2008;68:5206-15.
11. Redmond WL, Gough MJ, Weinberg AD. Ligation of the OX40 co-stimulatory receptor reverses self-Ag and tumor-induced CD8 T-cell anergy in vivo. Eur J Immunol 2009;39:2184-94.
12. Berendt MJ, North RJ: T-cell-mediated suppression of anti-tumor immunity. An explanation for progressive growth of an immunogenic tumor. J Exp Med 1980;151:69-80.
13. Bursuker I, North RJ. Generation and decay of the immune response to a progressive fibrosarcoma. II. Failure to demonstrate postexcision immunity after the onset of Tcell-mediated suppression of immunity. J Exp Med 1984;159:1312-21.
14. North RJ, Bursuker I. Generation and decay of the immune response to a progressive fibrosarcoma I. Ly-1+2- suppressor T cells down-regulate the generation of Ly-1-2+ effector T cells. J Exp Med 1984;159:1295-311.
15. Gorsch SM, Memoli VA, Stukel TA, Gold LI, Arrick BA. Immunohisto-chemical staining for transforming growth factor beta 1 associates with disease progression in human breast cancer. Cancer Res 1992;52:6949-52.
16. Robson H, Anderson E, James RD, Schofield PF: Transforming growth factor beta 1 expression in human colorectal tumours: an independent prognostic marker in a subgroup of poor prognosis patients. Br J Cancer 1996;74:753-8.
17. Rodeck U, Bossler A, Graeven U, Fox FE, Nowell PC, Knabbe C, et al. Transforming growth factor beta production and responsivenessinnormal human melanocytes and melanoma cells. Cancer Res 1994;54:575-81.
18. Donkor MK, Sarkar A, Savage PA, Franklin RA, Johnson LK, Jungbluth AA, et al. T cell surveillance of oncogene-induced prostate cancer is impeded by T cell-derived TGF-beta1 cytokine. Immunity 2011;35:123-34.
19. Flavell RA, Sanjabi S, Wrzesinski SH, Licona-Limon P: The polarization of immune cells in the tumour environment by TGFbeta. Nat Rev Immunol 2010;10:554-67.
20. Massague J: TGFbeta in cancer. Cell 2008;134:215-30.
21. Gorelik L, Constant S, Flavell RA. Mechanismoftransforming growth factor beta-induced inhibition of T helper type 1 differentiation. J Exp Med 2002;195:1499-505.
22. Thomas DA, Massague J. TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance. Cancer Cell 2005;8:369-80.
23. Huber S, Schramm C, Lehr HA, Mann A, Schmitt S, Becker C, et al. Cutting edge: TGF-beta signaling is required for the in vivo expansion and immunosuppressive capacity of regulatory CD4+CD25+ T cells. J Immunol 2004;173:6526-31.
24. Li MO, Sanjabi S, Flavell RA. Transforming growth factor-beta controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and -independent mechanisms. Immunity 2006;25:455-71.
25. Nam JS, Terabe M, Mamura M, Kang MJ, Chae H, Stuelten C, et al. An anti-transforming growth factor beta antibody suppresses metastasis via cooperative effects on multiple cell compartments. Cancer Res 2008;68: 3835-43.
26. Muraoka RS, Dumont N, Ritter CA, Dugger TC, Brantley DM, Chen J, et al. Blockade of TGF-beta inhibits mammary tumor cell viability, migration, and metastases. J Clin Invest 2002;109:1551-9.
27. Rausch MP, Hahn T, Ramanathapuram L, Bradley-Dunlop D, Mahadevan D, Mercado-Pimentel ME, et al. An orally active small molecule TGF-beta receptor I antagonist inhibits the growth of metastatic murine breast cancer. Anticancer Res 2009;29:2099-109.
28. Suzuki E, Kim S, Cheung HK, Corbley MJ, Zhang X, Sun L, et al. A novel small-molecule inhibitor oftransforming growth factor beta type I receptor kinase (SM16) inhibits murine mesothelioma tumor growth in vivo and prevents tumor recurrence after surgical resection. Cancer Res 2007;67: 2351-9.
29. Uhl M, Aulwurm S, Wischhusen J, Weiler M, Ma JY, Almirez R, et al. SD-208, a novel transforming growth factor beta receptor I kinase inhibitor, inhibits growth and invasiveness and enhances immunogenicity of murine and human glioma cells in vitro and in vivo. Cancer Res 2004;64:7954-61.
30. Wallace A, Kapoor V, Sun J, Mrass P, Weninger W, Heitjan DF, et al. Transforming growth factor-beta receptor blockade augments the effectiveness of adoptive T-cell therapy of established solid cancers. Clin Cancer Res 2008;14:3966-74.
31. Garrison K, Hahn T, Lee WC, Ling LE, Weinberg AD, Akporiaye ET. The small molecule TGF-beta signaling inhibitor SM16 synergizes with agonistic OX40 antibody to suppress established mammary tumors and reduce spontaneous metastasis. Cancer Immunol Immunother 2012; 61:511-21.
32. Yu H, Pardoll D, Jove R: STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer 2009;9:798-809.
33. Klinger M, Kim JK, Chmura SA, Barczak A, Erle DJ, Killeen N. Thymic OX40 expression discriminates cells undergoing strong responses to selection ligands. J Immunol 2009;182:4581-9.
34. Srinivas S, Watanabe T, Lin CS, William CM, Tanabe Y, Jessell TM, et al. Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus. BMC Dev Biol 2001;1:4.
35. Coussens LM, Werb Z. Inflammation and cancer. Nature 2002;420:860-7.
36. Frey AB, Monu N. Signaling defects in anti-tumor T cells. Immunol Rev 2008;222:192-205.
37. Luscher U, Filgueira L, Juretic A, Zuber M, Luscher NJ, Heberer M, et al. The pattern of cytokine gene expression in freshly excised human metastatic melanoma suggests a state of reversible anergy of tumor-infiltrating lymphocytes. Int J Cancer 1994;57:612-9.
38. Ohta A, Gorelik E, Prasad SJ, Ronchese F, Lukashev D, Wong MK, et al. A2A adenosine receptor protects tumors from antitumor T cells. Proc Natl Acad Sci U S A 2006;103:13132-7.
39. Dighe AS, Richards E, Old LJ, Schreiber RD: Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFN gamma receptors. Immunity 1994;1:447-56.
40. Kaplan DH, Shankaran V, Dighe AS, Stockert E, Aguet M, Old LJ, et al. Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci U S A 1998; 95:7556-61.
41. Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ, et al. IFNγ and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 2001;410:1107-11.
42. Street SE, Cretney E, Smyth MJ. Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis. Blood 2001;97:192-7.
43. Street SE, Trapani JA, MacGregor D, Smyth MJ. Suppression of lymphoma and epithelial malignancies effected by interferon gamma. J Exp Med 2002;196:129-34.
44. Redmond WL, Gough MJ, Charbonneau B, Ratliff TL, Weinberg AD. Defects in the acquisition of CD8 T cell effector function after priming with tumor or soluble antigen can be overcome by the addition of an OX40 agonist. J Immunol 2007;179:7244-53.
45. Gattinoni L, Klebanoff CA, Palmer DC, Wrzesinski C, Kerstann K, Yu Z, et al. Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8+ T cells. J Clin Invest 2005;115:1616-26.
46. Lee SW, Park Y, Song A, Cheroutre H, Kwon BS, Croft M. Functional dichotomy between OX40 and 4-1BB in modulating effector CD8 T cell responses. J Immunol 2006;177:4464-72.
47. Siegel AM, Heimall J, Freeman AF, Hsu AP, Brittain E, Brenchley JM, et al. A critical role for STAT3 transcription factor signalinginthe development and maintenance of human T cell memory. Immunity 2011;35:806-18.
48. Yu CR, Dambuza IM, Lee YJ, Frank GM, Egwuagu CE. STAT3 regulates proliferation and survival of CD8+ T cells: enhances effector responses to HSV-1 infection, and inhibits IL-10+ regulatory CD8+ T cells in autoimmune uveitis. Mediators Inflamm 2013;2013:359674.