IL-23 stabilizes an effector Treg cell program in the tumor microenvironment

Wertheimer, Tobias; Zwicky, Pascale; Rindlisbacher, Lukas; Sparano, Colin; Vermeer, Marijne; de Melo, Bruno Marcel Silva; Haftmann, Claudia; Rueckert, Tamina; Sethi, Aakriti; Schaerli, Stefanie; Huber, Anna; Ingelfinger, Florian; Xu, Caroline; Kim, Daehong; Haene, Philipp; Fonseca da Silva, Andre; Muschaweckh, Andreas; Nunez, Nicolas; Krishnarajah, Sinduya; Koehler, Natalie; Zeiser, Robert; Oukka, Mohamed; Korn, Thomas; Tugues, Sonia und Becher, Burkhard (2024): IL-23 stabilizes an effector Treg cell program in the tumor microenvironment. In: Nature Immunology, Vol. 25, No. 3

Abstract

Interleukin-23 (IL-23) is a proinflammatory cytokine mainly produced by myeloid cells that promotes tumor growth in various preclinical cancer models and correlates with adverse outcomes. However, as to how IL-23 fuels tumor growth is unclear. Here, we found tumor-associated macrophages to be the main source of IL-23 in mouse and human tumor microenvironments. Among IL-23-sensing cells, we identified a subset of tumor-infiltrating regulatory T (T-reg) cells that display a highly suppressive phenotype across mouse and human tumors. The use of three preclinical models of solid cancer in combination with genetic ablation of Il23r in T-reg cells revealed that they are responsible for the tumor-promoting effect of IL-23. Mechanistically, we found that IL-23 sensing represents a crucial signal driving the maintenance and stabilization of effector T-reg cells involving the transcription factor Foxp3. Our data support that targeting the IL-23/IL-23R axis in cancer may represent a means of eliciting antitumor immunity.

• Item Type: Journal article
• Faculties: Medicine > Munich Cluster for Systems Neurology (SyNergy)
• Subjects: 600 Technology > 610 Medicine and health
• Language: English
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198