TY - JOUR
TI - An intrinsic role of IL-33 in Treg cell–mediated tumor immunoevasion
AU - Hatzioannou, A.
AU - Banos, A.
AU - Sakelaropoulos, T.
AU - Fedonidis, C.
AU - Vidali, M.-S.
AU - Köhne, M.
AU - Händler, K.
AU - Boon, L.
AU - Henriques, A.
AU - Koliaraki, V.
AU - Georgiadis, P.
AU - Zoidakis, J.
AU - Termentzi, A.
AU - Beyer, M.
AU - Chavakis, T.
AU - Boumpas, D.
AU - Tsirigos, A.
AU - Verginis, P.
JO - Nature Immunology
PY - 2020
VL - 21
TODO - 1
SP - 75-85
PB - Institute of Geographic Sciences and Natural Resources Research
SN - 1529-2908, 1529-2916
TODO - 10.1038/s41590-019-0555-2
TODO - gamma interferon;  immunoglobulin enhancer binding protein;  interleukin 33;  monoclonal antibody;  monoclonal antibody 4F10;  monoclonal antibody RMP1-14;  receptor;  suppression of tumorigenicity 2 receptor;  transcription factor FOXP3;  transcription factor T bet;  unclassified drug;  gamma interferon;  Il1rl1 protein, mouse;  Il33 protein, mouse;  immunoglobulin enhancer binding protein;  interleukin 1 receptor like 1 protein;  interleukin 33, animal cell;  animal experiment;  animal model;  animal tissue;  Article;  cancer immunotherapy;  chromatin;  controlled study;  cytokine production;  epigenetics;  female;  gene locus;  in vivo study;  lymphocyte function;  male;  mouse;  neoplasm;  nonhuman;  nuclear reprogramming;  phenotype;  priority journal;  protein function;  regulatory T lymphocyte;  tumor escape;  tumor growth;  tumor microenvironment;  tumor regression;  upregulation;  animal;  C57BL mouse;  experimental melanoma;  genetics;  immunology;  knockout mouse;  metabolism;  regulatory T lymphocyte;  tumor cell line;  tumor escape, Animals;  Cell Line, Tumor;  Interferon-gamma;  Interleukin-1 Receptor-Like 1 Protein;  Interleukin-33;  Melanoma, Experimental;  Mice;  Mice, Inbred C57BL;  Mice, Knockout;  NF-kappa B;  T-Lymphocytes, Regulatory;  Tumor Escape
TODO - 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. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
ER -