| Autor: |
Eric Jou, Noe Rodriguez-Rodriguez, Ana-Carolina F. Ferreira, Helen E. Jolin, Paula A. Clark, Kovilen Sawmynaden, Michelle Ko, Jane E. Murphy, Jonathan Mannion, Christopher Ward, David J. Matthews, Simon J. A. Buczacki, Andrew N. J. McKenzie |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Science Immunology |
| ISSN: |
2470-9468 |
| DOI: |
10.1126/sciimmunol.abn0175 |
| Popis: |
Interleukin-25 (IL-25) and group 2 innate lymphoid cells (ILC2s) defend the host against intestinal helminth infection and are associated with inappropriate allergic reactions. IL-33–activated ILC2s were previously found to augment protective tissue-specific pancreatic cancer immunity. Here, we showed that intestinal IL-25–activated ILC2s created an innate cancer-permissive microenvironment. Colorectal cancer (CRC) patients with higher tumor IL25 expression had reduced survival and increased IL-25R–expressing tumor-resident ILC2s and myeloid-derived suppressor cells (MDSCs) associated with impaired antitumor responses. Ablation of IL-25 signaling reduced tumors, virtually doubling life expectancy in an Apc mutation–driven model of spontaneous intestinal tumorigenesis. Mechanistically, IL-25 promoted intratumoral ILC2s, which sustained tumor-infiltrating MDSCs to suppress antitumor immunity. Therapeutic antibody-mediated blockade of IL-25 signaling decreased intratumoral ILC2s, MDSCs, and adenoma/adenocarcinoma while increasing antitumor adaptive T cell and interferon-γ (IFN-γ)–mediated immunity. Thus, the roles of innate epithelium-derived cytokines IL-25 and IL-33 as well as ILC2s in cancer cannot be generalized. The protumoral nature of the IL-25–ILC2 axis in CRC highlights this pathway as a potential therapeutic target against CRC. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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