An intrinsic role of IL-33 in Treg cell-mediated tumor immunoevasion
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.
| Errataetall: |
CommentIn: Nat Immunol. 2020 Jan;21(1):11-13. - PMID 31822867 |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
|---|---|
| Enthalten in: |
Nature immunology - 21(2020), 1 vom: 16. Jan., Seite 75-85 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Hatzioannou, Aikaterini [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
82115-62-6 |
|---|
| Anmerkungen: |
Date Completed 15.04.2020 Date Revised 18.04.2022 published: Print-Electronic CommentIn: Nat Immunol. 2020 Jan;21(1):11-13. - PMID 31822867 Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41590-019-0555-2 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM30445253X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM30445253X | ||
| 003 | DE-627 | ||
| 005 | 20231225115022.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41590-019-0555-2 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1014.xml |
| 035 | |a (DE-627)NLM30445253X | ||
| 035 | |a (NLM)31844326 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Hatzioannou, Aikaterini |e verfasserin |4 aut | |
| 245 | 1 | 3 | |a An intrinsic role of IL-33 in Treg cell-mediated tumor immunoevasion |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 15.04.2020 | ||
| 500 | |a Date Revised 18.04.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: Nat Immunol. 2020 Jan;21(1):11-13. - PMID 31822867 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Il1rl1 protein, mouse |2 NLM | |
| 650 | 7 | |a Il33 protein, mouse |2 NLM | |
| 650 | 7 | |a Interleukin-1 Receptor-Like 1 Protein |2 NLM | |
| 650 | 7 | |a Interleukin-33 |2 NLM | |
| 650 | 7 | |a NF-kappa B |2 NLM | |
| 650 | 7 | |a Interferon-gamma |2 NLM | |
| 650 | 7 | |a 82115-62-6 |2 NLM | |
| 700 | 1 | |a Banos, Aggelos |e verfasserin |4 aut | |
| 700 | 1 | |a Sakelaropoulos, Theodore |e verfasserin |4 aut | |
| 700 | 1 | |a Fedonidis, Constantinos |e verfasserin |4 aut | |
| 700 | 1 | |a Vidali, Maria-Sophia |e verfasserin |4 aut | |
| 700 | 1 | |a Köhne, Maren |e verfasserin |4 aut | |
| 700 | 1 | |a Händler, Kristian |e verfasserin |4 aut | |
| 700 | 1 | |a Boon, Louis |e verfasserin |4 aut | |
| 700 | 1 | |a Henriques, Ana |e verfasserin |4 aut | |
| 700 | 1 | |a Koliaraki, Vasiliki |e verfasserin |4 aut | |
| 700 | 1 | |a Georgiadis, Panagiotis |e verfasserin |4 aut | |
| 700 | 1 | |a Zoidakis, Jerome |e verfasserin |4 aut | |
| 700 | 1 | |a Termentzi, Aikaterini |e verfasserin |4 aut | |
| 700 | 1 | |a Beyer, Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Chavakis, Triantafyllos |e verfasserin |4 aut | |
| 700 | 1 | |a Boumpas, Dimitrios |e verfasserin |4 aut | |
| 700 | 1 | |a Tsirigos, Aristotelis |e verfasserin |4 aut | |
| 700 | 1 | |a Verginis, Panayotis |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature immunology |d 2000 |g 21(2020), 1 vom: 16. Jan., Seite 75-85 |w (DE-627)NLM10805523X |x 1529-2916 |7 nnns |
| 773 | 1 | 8 | |g volume:21 |g year:2020 |g number:1 |g day:16 |g month:01 |g pages:75-85 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41590-019-0555-2 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 21 |j 2020 |e 1 |b 16 |c 01 |h 75-85 | ||