Instability of Helios-deficient Tregs is associated with conversion to a T-effector phenotype and enhanced antitumor immunity

Proceedings of the National Academy of Sciences of the United States of America

Volumn 113, Issue 22, 2016, Pages 6248-6253

  Nakagawa, Hidetoshi ^a,b   Sido, Jessica M ^a,b   Reyes, Edwin E ^a,b   Kiers, Valerie ^a   Cantor, Harvey ^a,b   Kim, Hye Jung ^a,b  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Effector cytokines; Inflammation; Treg stability; Tumor microenvironment

Indexed keywords

TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR HELIOS; UNCLASSIFIED DRUG; DNA BINDING PROTEIN; LYMPHOCYTE ANTIGEN RECEPTOR; ZFPN1A2 PROTEIN, MOUSE;

ANIMAL CELL; ARTICLE; CD4+ T LYMPHOCYTE; CONTROLLED STUDY; DOWN REGULATION; EFFECTOR CELL; MOUSE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; TUMOR IMMUNITY; TUMOR MICROENVIRONMENT; ANIMAL; HELPER CELL; IMMUNOLOGY; KNOCKOUT MOUSE; MELANOMA, EXPERIMENTAL; METABOLISM; PATHOLOGY; PHYSIOLOGY; T LYMPHOCYTE SUBPOPULATION; TUMOR ASSOCIATED LEUKOCYTE;

ANIMALS; DNA-BINDING PROTEINS; LYMPHOCYTES, TUMOR-INFILTRATING; MELANOMA, EXPERIMENTAL; MICE; MICE, KNOCKOUT; RECEPTORS, ANTIGEN, T-CELL; T-LYMPHOCYTE SUBSETS; T-LYMPHOCYTES, HELPER-INDUCER; T-LYMPHOCYTES, REGULATORY; TRANSCRIPTION FACTORS;

EID: 84971602146     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1604765113     Document Type: Article

References (25)

1. Scanlan MJ, Gure AO, Jungbluth AA, Old LJ, Chen YT (2002) Cancer/testis antigens: An expanding family of targets for cancer immunotherapy. Immunol Rev 188:22-32.
2. Nishikawa H, Sakaguchi S (2014) Regulatory T cells in cancer immunotherapy. Curr Opin Immunol 27:1-7.
3. Kurtulus S, et al. (2015) TIGIT predominantly regulates the immune response via regulatory T cells. J Clin Invest 125(11):4053-4062.
4. Sugiyama D, et al. (2013) Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+ regulatory T cells, evoking antitumor immune responses in humans. Proc Natl Acad Sci USA 110(44):17945-17950.
5. Yamaguchi T, et al. (2007) Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor. Immunity 27(1):145-159.
6. Kim HJ, et al. (2015) Stable inhibitory activity of regulatory T cells requires the transcription factor Helios. Science 350(6258):334-339.
7. Sebastian M, et al. (2016) Helios controls a limited subset of regulatory T cell functions. J Immunol 196(1):144-155.
8. Liston A, Gray DH (2014) Homeostatic control of regulatory T cell diversity. Nat Rev Immunol 14(3):154-165.
9. Sakuishi K, et al. (2013) TIM3(+)FOXP3(+) regulatory T cells are tissue-specific promoters of T-cell dysfunction in cancer. OncoImmunology 2(4):e23849.
10. Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917):860-867.
11. Cai Q, Dierich A, Oulad-Abdelghani M, Chan S, Kastner P (2009) Helios deficiency has minimal impact on T cell development and function. J Immunol 183(4):2303-2311.
12. Feng Y, et al. (2014) Control of the inheritance of regulatory T cell identity by a cis element in the Foxp3 locus. Cell 158(4):749-763.
13. Shimizu J, Yamazaki S, Takahashi T, Ishida Y, Sakaguchi S (2002) Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat Immunol 3(2):135-142.
14. Schaer DA, et al. (2013) GITR pathway activation abrogates tumor immune suppression through loss of regulatory T cell lineage stability. Cancer Immunol Res 1(5):320-331.
15. Murphy JT, et al. (2014) Anaphylaxis caused by repetitive doses of a GITR agonist monoclonal antibody in mice. Blood 123(14):2172-2180.
16. Mahoney KM, Rennert PD, Freeman GJ (2015) Combination cancer immunotherapy and new immunomodulatory targets. Nat Rev Drug Discov 14(8):561-584.
17. Simpson TR, et al. (2013) Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. J Exp Med 210(9):1695-1710.
18. Francisco LM, et al. (2009) PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med 206(13):3015-3029.
19. Page DB, Postow MA, Callahan MK, Allison JP, Wolchok JD (2014) Immune modulation in cancer with antibodies. Annu Rev Med 65:185-202.
20. Malchow S, et al. (2013) Aire-dependent thymic development of tumor-associated regulatory T cells. Science 339(6124):1219-1224.
21. Quezada SA, et al. (2010) Tumor-reactive CD4(+) T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts. J Exp Med 207(3):637-650.
22. Hirschhorn-Cymerman D, et al. (2012) Induction of tumoricidal function in CD4+ T cells is associated with concomitant memory and terminally differentiated phenotype. J Exp Med 209(11):2113-2126.
23. Malandro N, et al. (2016) Clonal abundance of tumor-specific CD4(+) T cells potentiates efficacy and alters susceptibility to exhaustion. Immunity 44(1):179-193.
24. Xiao X, et al. (2015) GITR subverts Foxp3(+) Tregs to boost Th9 immunity through regulation of histone acetylation. Nat Commun 6:8266.
25. Thornton AM, et al. (2010) Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J Immunol 184(7):3433-3441.