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

Abstract

Background Type 2 innate lymphoid cells (ILC2s), characterized by secreting 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. Methods ILC2s were sorted from the spleen using microbeads combined with flow cytometry and tumor infiltrating CD8+ T cells were isolated from tumor tissue by microbeads. Flow cytometry and immunofluorescence were used to detect the percentage of ILC2s and CD8+ T cells in the spleen and CRC tissue. Effects of IL-9 and IL-9-stimulated CD8+ T cells on CT26 cells were measured by proliferation, apoptosis, and migration assays in vitro. GEPIA was used to detect the ILC2s chemokines in CRC tissue and adjacent normal tissue. Results We found that ILC2s were increased in CRC tissue compared with the adjacent normal tissue. In vitro experiments showed that IL-9 could activate CD8+ T cells to promote the death of CT26 cells. ILC2s were the main IL-9-secreting cells in CRC tissue as shown by flow cytometry analysis. In vivo experiments showed that neutralizing ILC2s promoted the tumor growth, while tumor inhibition occurred by intravenous injection of IL-9. Conclusions Our results demonstrated that ILC2-derived IL-9 activated CD8+ T cells to promote anti-tumor effects in CRC.

Innate Lymphoid Cells in Tissue Homeostasis and Disease Pathogenesis

“…In addition, in a lung metastatic melanoma model, ILC2s produce IL-5, thereby activating eosinophils and increasing their anti-tumor response (Ikutani et al, 2012). Moreover, ILC2s produce IL-9, which is important to suppress metastasis of cancer cells, in tumor microenvironment (Park et al, 2020;Wan et al, 2021).…”