An intrinsic role of IL-33 in Treg cell–mediated tumor immunoevasion

Autor: Maria-Sophia Vidali, Louis Boon, Aggelos Banos, Aikaterini Termentzi, Triantafyllos Chavakis, Maren Köhne, Panayotis Verginis, Vasiliki Koliaraki, Aikaterini Hatzioannou, Dimitrios T. Boumpas, Constantinos Fedonidis, Marc Beyer, Theodore Sakelaropoulos, Jerome Zoidakis, Ana Henriques, Panagiotis Georgiadis, Aristotelis Tsirigos, Kristian Händler
Rok vydání: 2019
Předmět:
0301 basic medicine
metabolism [Interleukin-1 Receptor-Like 1 Protein]
immunology [Tumor Escape]
medicine.medical_treatment
Immunology
Il33 protein
mouse
chemical and pharmacologic phenomena
Biology
medicine.disease_cause
immunology [Melanoma
Experimental]
genetics [Interleukin-33]
Autoimmunity
Mice
Interferon-gamma
03 medical and health sciences
0302 clinical medicine
immunology [Interferon-gamma]
Cancer immunotherapy
Interferon
Cell Line
Tumor
medicine
Animals
Immunology and Allergy
ddc:610
Receptor
Mice
Knockout
NF-kappa B
Interleukin
hemic and immune systems
Il1rl1 protein
mouse
Immunotherapy
Interleukin-33
Interleukin-1 Receptor-Like 1 Protein
3. Good health
Chromatin
Mice
Inbred C57BL
Interleukin 33
030104 developmental biology
genetics [Interferon-gamma]
Cancer research
metabolism [NF-kappa B]
immunology [Interleukin-33]
immunology [T-Lymphocytes
Regulatory]
030215 immunology
medicine.drug
Zdroj: Nature immunology 21(1), 75-85 (2019). doi:10.1038/s41590-019-0555-2
Nature Immunology
ISSN: 1529-2916
1529-2908
DOI: 10.1038/s41590-019-0555-2
Popis: 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.
Databáze: OpenAIRE
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