Mouse Macrophage galactose-type lectin (mMGL)1 receptor exhibits immunosuppressive and inflammatory properties in colorectal cancer 4000

Abstract Description Cancer-associated aberrant glycosylation can be detected by the MGL receptor; however, whether this interaction enhances or deadens cancer development has not been well established. To determine the role of mouse MGL1 in colitis-associated colon cancer (CAC), azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced tumor development was compared between Mgl1 knockout (Mgl1-/-) mice and their wild-type (WT) littermates. At 75 days post-CAC induction, colon tumor tissue contained more highly glycosylated proteins, potential ligands for the mMGL1 receptor, than colon - healthy tissue. The Mgl1-/- CAC mice presented fewer disease activity indices and fewer colonic tumors. The colonic crypt architecture was less damaged, and mucin production was more significant than WT CAC mice. Furthermore, Mgl1-/- CAC mice displayed higher percentages of CD4+ and CD8+ T cells in the peripheral blood, and colonic lamina propria, while lower percentages of myeloid - derived suppressor cells (MDSCs) were detected. Less macrophage and natural killer cell infiltration, as well as lower levels of iNOS and arginase, were found in the tumor microenvironment of Mgl1-/- CAC mice compared to WT mice. Moreover, the colonic ERK 1/2 signalling was significantly reduced in Mgl1-/- CAC mice compared with WT CAC mice. These results suggest that mMGL1 may recognize aberrant glycosylation which may trigger an inflammatory microenvironment and favor colon tumorigenesis. Funding Sources Partially supported by PAPIIT IN217021 Partially supported byCONAHCyT CF-2019/21067 Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)