Newly isolated Lactobacillus fermentum strain promotes IFN-γ secreting CD8+ T cells for enhanced anti-cancer immunity 2851

Abstract Description Immune checkpoint inhibitors (ICIs) have shown significant clinical efficacy across various cancer types. However, patients with solid tumors, such as colorectal cancer, often exhibit limited responses to ICIs. Recent studies have suggested the gut microbiota may enhance cancer immunotherapy, but the microbial molecules responsible for these effects and their mechanisms remain unclear. In this study, we aimed to identify microbial molecules that synergize with ICIs to enhance anti-cancer immunity. We screened various probiotic strains for bacteria capable of stimulating anti-cancer immune responses and identified Lactobacillus fermentum MI37, isolated from the feces of healthy volunteers. MI37 strongly induced IFN-γ expression from splenic cells while minimally affecting IL-10 expression. Oral administration of MI37, in combination with anti-PD-1 therapy, significantly enhanced anti-tumor immunity in a syngeneic tumor mouse model. This combination therapy increased tumor-infiltrating cytotoxic T lymphocytes (CTLs) and upregulated inflammation-associated transcripts within the tumor. Notably, heat-inactivated MI37 also stimulated IFN-γ production in splenic cells, similar to live MI37, and reduced tumor size in tumor-bearing mice. These findings suggest that the structural components of MI37 may act as mediators of anti-cancer immune responses, offering a promising avenue for improving the efficacy of cancer immunotherapy. Funding Sources Supported by RS-2024-00338401; the Basic Science Research Program through the National Research Foundation of Korea (NRF). Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)