TGF-β and VEGF cooperatively control the immunotolerant tumor environment and the efficacy of cancer immunotherapies

JCI Insight

Volumn 1, Issue 9, 2016, Pages

  Courau, Tristan ^a,b   Nehar Belaid, Djamel ^a,b   Florez, Laura ^a,b   Levacher, Béatrice ^a,b   Vazquez, Thomas ^a,b   Brimaud, Faustine ^a,b,c   Bellier, Bertrand ^a,b   Klatzmann, David ^a,b,c  

^a SORBONNE UNIVERSITÉ   (France)

^b Sorbonne Université   (France)

^c PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85055598418     PISSN: None     EISSN: 23793708     Source Type: Journal    
DOI: 10.1172/jci.insight.85974     Document Type: Article

References (58)

1. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140(6):883–899.
2. Zitvogel L, Apetoh L, Ghiringhelli F, André F, Tesniere A, Kroemer G. The anticancer immune response: indispensable for therapeutic success? J Clin Invest. 2008;118(6):1991–2001.
3. Billiard F, et al. Regulatory and effector T cell activation levels are prime determinants of in vivo immune regulation. J Immunol. 2006;177(4):2167–2174.
4. + T cells: a common basis between tumor immunity and autoimmunity. J Immunol. 1999;163(10):5211–5218.
5. Onizuka S, Tawara I, Shimizu J, Sakaguchi S, Fujita T, Nakayama E. Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. Cancer Res. 1999;59(13):3128–3133.
6. Galon J, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313(5795):1960–1964.
7. Curiel TJ, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004;10(9):942–949.
8. Nishikawa H, Sakaguchi S. Regulatory T cells in tumor immunity. Int J Cancer. 2010;127(4):759–767.
9. Curran MA, Montalvo W, Yagita H, Allison JP. 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 U S A. 2010;107(9):4275–4280.
10. Wolchok JD, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369(2):122–133.
11. Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell. 2015;27(4):450–461.
12. Johnston RJ, et al. The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function. Cancer Cell. 2014;26(6):923–937.
13. Wang X, et al. IL-36γ transforms the tumor microenvironment and promotes type 1 lymphocyte-mediated antitumor immune responses. Cancer Cell. 2015;28(3):296–306.
14. Facciabene A, Motz GT, Coukos G. T-regulatory cells: key players in tumor immune escape and angiogenesis. Cancer Res. 2012;72(9):2162–2171.
15. Ondondo B, Jones E, Godkin A, Gallimore A. Home sweet home: the tumor microenvironment as a haven for regulatory T cells. Front Immunol. 2013;4:197.
16. Nehar-Belaid D, Courau T, Dérian N, Florez L, Ruocco MG, Klatzmann D. Regulatory T cells orchestrate similar immune evasion of fetuses and tumors in mice. J Immunol. 2016;196(2):678–690.
17. Darrasse-Jèze G, et al. Tumor emergence is sensed by self-specific CD44hi memory Tregs that create a dominant tolerogenic environment for tumors in mice. J Clin Invest. 2009;119(9):2648–2662.
18. Motz GT, Coukos G. Deciphering and reversing tumor immune suppression. Immunity. 2013;39(1):61–73.
19. Rabinovich GA, Gabrilovich D, Sotomayor EM. Immunosuppressive strategies that are mediated by tumor cells. Annu Rev Immunol. 2007;25:267–296.
20. Johnson BF, Clay TM, Hobeika AC, Lyerly HK, Morse MA. Vascular endothelial growth factor and immunosuppression in cancer: current knowledge and potential for new therapy. Expert Opin Biol Ther. 2007;7(4):449–460.
21. Tian M, Neil JR, Schiemann WP. Transforming growth factor-β and the hallmarks of cancer. Cell Signal. 2011;23(6):951–962.
22. Olsson A-K, Dimberg A, Kreuger J, Claesson-Welsh L. VEGF receptor signalling - in control of vascular function. Nat Rev Mol Cell Biol. 2006;7(5):359–371.
23. Gabrilovich DI, et al. Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med. 1996;2(10):1096–1103.
24. Nagaraj S, et al. Regulatory myeloid suppressor cells in health and disease. Cancer Res. 2009;69(19):7503–7506.
25. Li B, et al. Vascular endothelial growth factor blockade reduces intratumoral regulatory T cells and enhances the efficacy of a GM-CSF-secreting cancer immunotherapy. Clin Cancer Res. 2006;12(22):6808–6816.
26. Terme M, et al. VEGFA-VEGFR pathway blockade inhibits tumor-induced regulatory T-cell proliferation in colorectal cancer. Cancer Res. 2013;73(2):539–549.
27. + T cells in tumors. J Exp Med. 2015;212(2):139–148.
28. Chang CH, et al. Metabolic competition in the tumor microenvironment is a driver of cancer progression. Cell. 2015;162(6):1229–1241.
29. Siska PJ, Rathmell JC. T cell metabolic fitness in antitumor immunity. Trends Immunol. 2015;36(4):257–264.
30. Huang H, et al. VEGF suppresses T-lymphocyte infiltration in the tumor microenvironment through inhibition of NF-κBinduced endothelial activation. FASEB J. 2015;29(1):227–238.
31. Bierie B, Moses HL. Tumour microenvironment: TGFbeta: the molecular Jekyll and Hyde of cancer. Nat Rev Cancer. 2006;6(7):506–520.
32. 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(3):455–471.
33. Adeegbe DO, Nishikawa H. Natural and induced T regulatory cells in cancer. Front Immunol. 2013;4:190.
34. + regulatory T cells. J Exp Med. 2005;201(7):1061–1067.
35. + regulatory T cell proliferation. J Exp Med. 2005;202(7):919–929.
36. Massagué J. TGFβ in Cancer. Cell. 2008;134(2):215–230.
37. Flavell RA, Sanjabi S, Wrzesinski SH, Licona-Limón P. The polarization of immune cells in the tumour environment by TGFbeta. Nat Rev Immunol. 2010;10(8):554–567.
38. Rubinson DA, et al. A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interference. Nat Genet. 2003;33(3):401–406.
39. Bergot AS, Durgeau A, Levacher B, Colombo BM, Cohen JL, Klatzmann D. Antigen quality determines the efficiency of antitumor immune responses generated in the absence of regulatory T cells. Cancer Gene Ther. 2010;17(9):645–654.
40. Gene Ontology Consortium. Creating the gene ontology resource: design and implementation. Genome Res. 2001;11(8):1425–1433.
41. Shannon P, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498–2504.
42. Merico D, Isserlin R, Stueker O, Emili A, Bader GD. Enrichment map: a network-based method for gene-set enrichment visualization and interpretation. PLoS ONE. 2010;5(11):e13984.
43. Pham HP, Dérian N, Chaara W, Bellier B, Klatzmann D, Six A. A novel strategy for molecular signature discovery based on independent component analysis. Int J Data Min Bioinform. 2014;9(3):277–304.
44. + regulatory T cells in the steady state. J Exp Med. 2003;198(5):737–746.
45. Tanaka H, et al. Transforming growth factor β signaling inhibitor, SB-431542, induces maturation of dendritic cells and enhances anti-tumor activity. Oncol Rep. 2010;24(6):1637–1643.
46. Waghabi MC, et al. Pharmacological inhibition of transforming growth factor beta signaling decreases infection and prevents heart damage in acute Chagas’ disease. Antimicrob Agents Chemother. 2009;53(11):4694–4701.
47. Bhaskaran N, Quigley C, Weinberg A, Huang A, Popkin D, Pandiyan P. Transforming growth factor-β1 sustains the survival of Foxp3(+) regulatory cells during late phase of oropharyngeal candidiasis infection [published online ahead of print November 4, 2015]. Mucosal Immunol. doi: 10.1038/mi.2015.115.
48. Somasundaram R, Herlyn M. Nivolumab in combination with ipilimumab for the treatment of melanoma. Expert Rev Anticancer Ther. 2015;15(10):1135–1141.
49. Vanneman M, Dranoff G. Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer. 2012;12(4):237–251.
50. Chouaib S, Messai Y, Couve S, Escudier B, Hasmim M, Noman MZ. Hypoxia promotes tumor growth in linking angiogenesis to immune escape. Front Immunol. 2012;3:21.
51. Hodi FS, et al. Bevacizumab plus ipilimumab in patients with metastatic melanoma. Cancer Immunol Res. 2014;2(7):632–642.
52. Marzo AL, et al. Tumor antigens are constitutively presented in the draining lymph nodes. J Immunol. 1999;162(10):5838–5845.
53. Desjardins D, et al. Recombinant retrovirus-like particle forming DNA vaccines in prime-boost immunization and their use for hepatitis C virus vaccine development. J Gene Med. 2009;11(4):313–325.
54. Naldini L, et al. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science. 1996;272(5259):263–267.
55. Li H, et al. Vaccination with B16 tumor cell lysate plus recombinant Mycobacterium tuberculosis Hsp70 induces antimelanoma effect in mice. Cancer Biother Radiopharm. 2010;25(2):185–191.
56. + regulatory/suppressor T cells prevent allogeneic fetus rejection in mice. Immunol Lett. 2006;102(1):106–109.
57. Chaput N, et al. Regulatory T cells prevent CD8 T cell maturation by inhibiting CD4 Th cells at tumor sites. J Immunol. 2007;179(8):4969–4978.
58. Subramanian A, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102(43):15545–15550.