| First Author | Li P | Year | 2024 |
| Journal | Int Immunopharmacol | Volume | 128 |
| Pages | 111464 | PubMed ID | 38224627 |
| Mgi Jnum | J:344562 | Mgi Id | MGI:7578643 |
| Doi | 10.1016/j.intimp.2023.111464 | Citation | Li P, et al. (2024) Deletion of IL-27p28 induces CD8 T cell immunity against colorectal tumorigenesis. Int Immunopharmacol 128:111464 |
| abstractText | Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, characterized by molecular and clinical heterogeneity. Interleukin (IL)-27, a heterodimeric cytokine composed of p28 and EBI3 subunits, has been reported to exert potent antitumor activity in several cancer models. However, the precise role of IL-27 in the pathogenesis of CRC remains unclear. Here, we show that during the azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC development, IL-27p28 levels are dramatically increased in peripheral blood and tumor tissues, and the cytokine is mainly produced by tumor-infiltrating myeloid cells. IL-27p28 deficient mice display tumor resistances in both inflammation-associated CRC model and syngeneic MC38 colon cancer model. Administration with IL-27p28 neutralizing antibody also reduces the tumor formation in AOM/DSS-treated mice. Mechanically, CD8(+) T cells in IL-27p28(-/-) mice exhibit enhanced tumor infiltration and cytotoxicity, which can be largely attributed to activation of the Akt/mTOR signaling pathway. Furthermore, selective depletion of CD8(+) T cells in IL-27p28(-/-) mice markedly accelerate tumor growth and almost abrogate the protective effects of IL-27p28 deficiency. Most interestingly, the expression of IL-27p28 is also upregulated in tumor tissues of CRC patients and those with high expression of IL-27p28 tend to have a poorer overall survival. Our results suggest that loss of IL-27p28 suppresses colorectal tumorigenesis by augmenting CD8(+) T cell-mediated anti-tumor immunity. Targeting IL-27p28 could be developed as a novel strategy for the treatment of colorectal cancers. |
