ILC2-derived IL-9 inhibits colorectal cancer progression by activating CD8+ T cells

Group 2 innate lymphoid cells (ILC2s), characterized by secretion of type 2 cytokines, regulate multiple immune responses. ILC2s are found in different tumor tissues, and ILC2-derived interleukin (IL)-4, IL-5, and IL-13 act on the cells in tumor microenvironment to participate in tumor progression. ILC2s are abundant in colorectal cancer (CRC) tissue, but the role of ILC2s in CRC remains unclear. In this study, we found that the percentage of ILC2s was higher in CRC tissue than in the adjacent normal tissue and that these ILC2s were the dominant IL-9-secreting cell-subsets in CRC tissue, as shown by flow cytometry analysis. ILC2s-derived IL-9 could activate CD8⁺ T cells to inhibit tumor growth, while anti-IL-9 reversed this effect. In vivo experiments showed that neutralizing ILC2s promoted tumor growth, while tumor inhibition occurred by intravenous injection of IL-9. In conclusion, our results demonstrated that ILC2-derived IL-9 could activate CD8⁺ T cells to promote anti-tumor effects in CRC.