The effect of MGL-2 C-type lectin receptor deficiency and the associated gut microbiota dysbiosis on tumor progression

Abstract

The gut microbiota plays a vital role in host health and disease, with dysbiosis being associated with various illnesses, such as cancer. Gut microbiota also impact the effectiveness of anti-tumor therapeutics, including immune checkpoint blockades. Macrophage galactose/N-acetyl- galactosamine (Gal/GalNAc)-specific lectin-2 (MGL-2) belongs to C-type lectin receptors (CLRs) that are expressed on mononuclear phagocytic cell and regulates adaptive immune responses to tumor cells. MGL-2 interacts with the GalNAc antigen, found in tumor cells, contributing to tumor progression and impacting patient survival. Bacterial cell walls display diverse glycan structures, making them a target for CLRs. MGL-2 also recognize the bacterial surface glycans of various pathogenic and commensal microbes in the intestine and skin. However, it remains unclear whether MGL-2-mediated signaling derived from gut microbes plays a role in tumor progression. Here, I investigated the impact of MGL-2 deficiency on tumor progression in solid and colitis-associated colorectal tumor models. I revealed that MGL-2 deficiency significantly accelerated tumor growth, which is associated with reduced tumor infiltration of CD8+ T cells and impaired cytokine production. Notably, antibiotics treatment effectively ameliorated the facilitated tumor growth observed in MGL-2-deficient mice. Furthermore, our study identified alterations in the gut microbiota composition in MGL-2 deficient mice. These results highlight the role of MGL-2 in the complex interplay between the immune response and the gut microbiota in colorectal cancer progression.