Details

Autor(en) / Beteiligte

• Kiss, Máté
• Vande Walle, Lieselotte
• Saavedra, Pedro H V
• Lebegge, Els
• Van Damme, Helena
• Murgaski, Aleksandar
• Qian, Junbin
• Ehling, Manuel
• Pretto, Samantha
• Bolli, Evangelia
• Keirsse, Jiri
• Bardet, Pauline M R
• Arnouk, Sana M
• Elkrim, Yvon
• Schmoetten, Maryse
• Brughmans, Jan
• Debraekeleer, Ayla
• Fossoul, Amelie
• Boon, Louis
• Raes, Geert
• van Loo, Geert
• Lambrechts, Diether
• Mazzone, Massimiliano
• Beschin, Alain
• Wullaert, Andy
• Lamkanfi, Mohamed
• Van Ginderachter, Jo A
• Laoui, Damya

Titel

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

Ist Teil von

• Cancer immunology research, 2021-03, Vol.9 (3), p.309-323

Ort / Verlag

United States

Erscheinungsjahr

2021

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.