Low miR-16 expression induces regulatory CD4(+)NKG2D(+) T cells involved in colorectal cancer progression

xlomafota13 shared this article with you from Inoreader Low miR-16 expression induces regulatory CD4(+)NKG2D(+) T cells involved in colorectal cancer progression Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1540-1556. eCollection 2021. ABSTRACT MiR-15a/16 is a member of the miRNA cluster that exhibits tumor suppression and immune modulation via targeting multiple genes. Decreased miR-15a/16 expression is involved in many cancer cells. Here, miR-16 had decreased expression in NK1.1-CD4+NKG2D+ T cells and bound with the 3'-UTR of NKG2D gene. MiR-15a/16-deficient mice had many CD4+NKG2D+ T cells, which produced TGF-β1 and IL-10 and inhibited the IFN-γ production of CD8+ T cells. Adoptive transfer of NK1.1-CD4+NKG2D+ T cells from miR-15a/16-deficient mice promoted tumor growth in vivo. However, no changes for NK1.1-CD4+NKG2D+ T cells were found in the miR-15a/16-transgenic mice. Although the miR-15a/16 transgenic mice transplanted with B16BL6 or MC38 cells exhibi ted rapid growth, these tumor-bearing mice did not show changes in NK1.1-CD4+NKG2D+ T cell distributions in either spleens or tumors. When NK1.1-CD4+ T cells were stimulated by α-CD3/sRAE-1 ex vivo, the NKG2D expression was difficult to induce in the T cells of miR-15a/16-transgenic mice. Finally, increased frequencies of regulatory CD4+NKG2D+ T cells with low miR-16 levels were observed in patients with late-stage colorectal cancer (Duke's C, D). Thus, miR-16 modulates NK1.1-CD4+NKG2D+ T cell functions via targeting NKG2D. Low miR-16 expression in CD4+ T cells induces the regulatory CD4+NKG2D+ T subpopulation, which promotes tumor evasion via the secretion of immune-suppressive molecules. PMID:33948372 | PMC:PMC8085839 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.