An intrinsic role of IL-33 in Treg cell-mediated tumor immunoevasion.
Nat Immunol
; 21(1): 75-85, 2020 01.
Article
em En
| MEDLINE
| ID: mdl-31844326
ABSTRACT
Regulatory T (Treg) cells accumulate into tumors, hindering the success of cancer immunotherapy. Yet, therapeutic targeting of Treg cells shows limited efficacy or leads to autoimmunity. The molecular mechanisms that guide Treg cell stability in tumors remain elusive. In the present study, we identify a cell-intrinsic role of the alarmin interleukin (IL)-33 in the functional stability of Treg cells. Specifically, IL-33-deficient Treg cells demonstrated attenuated suppressive properties in vivo and facilitated tumor regression in a suppression of tumorigenicity 2 receptor (ST2) (IL-33 receptor)-independent fashion. On activation, Il33-/- Treg cells exhibited epigenetic re-programming with increased chromatin accessibility of the Ifng locus, leading to elevated interferon (IFN)-γ production in a nuclear factor (NF)-κB-T-bet-dependent manner. IFN-γ was essential for Treg cell defective function because its ablation restored Il33-/- Treg cell-suppressive properties. Importantly, genetic ablation of Il33 potentiated the therapeutic effect of immunotherapy. Our findings reveal a new and therapeutically important intrinsic role of IL-33 in Treg cell stability in cancer.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Melanoma Experimental
/
Interferon gama
/
Linfócitos T Reguladores
/
Evasão Tumoral
/
Interleucina-33
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Nat Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Grécia