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IL1β Promotes Immune Suppression in the Tumor Microenvironment Independent of the Inflammasome and Gasdermin D.

التفاصيل البيبلوغرافية
العنوان: IL1β Promotes Immune Suppression in the Tumor Microenvironment Independent of the Inflammasome and Gasdermin D.
المؤلفون: Kiss M; Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.; Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium., Vande Walle L; VIB Center for Inflammation Research, Ghent, Belgium.; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium., Saavedra PHV; VIB Center for Inflammation Research, Ghent, Belgium.; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium., Lebegge E; Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.; Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium., Van Damme H; Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.; Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium., Murgaski A; Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.; Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium., Qian J; Laboratory of Translational Genetics, VIB Center for Cancer Biology, Leuven, Belgium.; Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium., Ehling M; Laboratory of Tumor Inflammation and Angiogenesis, VIB Center for Cancer Biology, Leuven, Belgium.; Laboratory of Tumor Inflammation and Angiogenesis, Department of Oncology, KU Leuven, Leuven, Belgium., Pretto S; Laboratory of Tumor Inflammation and Angiogenesis, VIB Center for Cancer Biology, Leuven, Belgium.; Laboratory of Tumor Inflammation and Angiogenesis, Department of Oncology, KU Leuven, Leuven, Belgium., Bolli E; Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.; Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium., Keirsse J; Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.; Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium., Bardet PMR; Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.; Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium., Arnouk SM; Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.; Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium., Elkrim Y; Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.; Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium., Schmoetten M; Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.; Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium., Brughmans J; Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.; Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium., Debraekeleer A; Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.; Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium., Fossoul A; VIB Center for Inflammation Research, Ghent, Belgium.; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium., Boon L; Polpharma Biologics, Utrecht, the Netherlands., Raes G; Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.; Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium., van Loo G; VIB Center for Inflammation Research, Ghent, Belgium.; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium., Lambrechts D; Laboratory of Translational Genetics, VIB Center for Cancer Biology, Leuven, Belgium.; Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium., Mazzone M; Laboratory of Tumor Inflammation and Angiogenesis, VIB Center for Cancer Biology, Leuven, Belgium.; Laboratory of Tumor Inflammation and Angiogenesis, Department of Oncology, KU Leuven, Leuven, Belgium., Beschin A; Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.; Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium., Wullaert A; VIB Center for Inflammation Research, Ghent, Belgium.; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium., Lamkanfi M; VIB Center for Inflammation Research, Ghent, Belgium.; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium., Van Ginderachter JA; Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium. dlaoui@vub.be jo.van.ginderachter@vub.be.; Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium., Laoui D; Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium. dlaoui@vub.be jo.van.ginderachter@vub.be.; Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
المصدر: Cancer immunology research [Cancer Immunol Res] 2021 Mar; Vol. 9 (3), pp. 309-323. Date of Electronic Publication: 2020 Dec 23.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 101614637 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2326-6074 (Electronic) Linking ISSN: 23266066 NLM ISO Abbreviation: Cancer Immunol Res Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Philadelphia, PA : American Association for Cancer Research, [2013]-
مواضيع طبية MeSH: Tumor Escape*, Interleukin-1beta/*metabolism , Neoplasms/*immunology , Neutrophils/*immunology , Tumor Microenvironment/*immunology, Animals ; Cell Communication/immunology ; Disease Models, Animal ; Female ; Humans ; Inflammasomes/immunology ; Inflammasomes/metabolism ; Interleukin-1beta/genetics ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Lymphocytes, Tumor-Infiltrating/immunology ; Mice ; Mice, Knockout ; Neoplasms/pathology ; Neutrophils/metabolism ; Phosphate-Binding Proteins/genetics ; Phosphate-Binding Proteins/metabolism ; T-Lymphocytes, Cytotoxic/immunology ; Tumor-Associated Macrophages/immunology
مستخلص: IL1β is a central mediator of inflammation. Secretion of IL1β typically requires proteolytic maturation by the inflammasome and formation of membrane pores by gasdermin D (GSDMD). Emerging evidence suggests an important role for IL1β in promoting cancer progression in patients, but the underlying mechanisms are ill-defined. Here, we have shown a key role for IL1β in driving tumor progression in two distinct mouse tumor models. Notably, activation of the inflammasome, caspase-8, as well as the pore-forming proteins GSDMD and mixed lineage kinase domain-like protein in the host were dispensable for the release of intratumoral bioactive IL1β. Inflammasome-independent IL1β release promoted systemic neutrophil expansion and fostered accumulation of T-cell-suppressive neutrophils in the tumor. Moreover, IL1β was essential for neutrophil infiltration triggered by antiangiogenic therapy, thereby contributing to treatment-induced immunosuppression. Deletion of IL1β allowed intratumoral accumulation of CD8 + effector T cells that subsequently activated tumor-associated macrophages. Depletion of either CD8 + T cells or macrophages abolished tumor growth inhibition in IL1β-deficient mice, demonstrating a crucial role for CD8 + T-cell-macrophage cross-talk in the antitumor immune response. Overall, these results support a tumor-promoting role for IL1β through establishing an immunosuppressive microenvironment and show that inflammasome activation is not essential for release of this cytokine in tumors.
(©2020 American Association for Cancer Research.)
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المشرفين على المادة: 0 (Gsdmd protein, mouse)
0 (IL1B protein, mouse)
0 (Inflammasomes)
0 (Interleukin-1beta)
0 (Intracellular Signaling Peptides and Proteins)
0 (Phosphate-Binding Proteins)
تواريخ الأحداث: Date Created: 20201228 Date Completed: 20210726 Latest Revision: 20210726
رمز التحديث: 20240628
DOI: 10.1158/2326-6066.CIR-20-0431
PMID: 33361087
قاعدة البيانات: MEDLINE
الوصف
تدمد:2326-6074
DOI:10.1158/2326-6066.CIR-20-0431