Engineered bacteria remodel tumor microenvironment to enhance CD8+ T cell-mediated immunity 2552

Abstract Description The immunosuppressive nature of the tumor microenvironment (TME) presents a major obstacle to effective cancer immunotherapy. Our previous studies demonstrated that engineered bacteria could remodel the TME, enhancing the infiltration and activity of cytotoxic CD8+ T cells (CTLs) and leading to tumor reduction in murine colorectal cancer models. However, this bacterial strain was initially limited to efficacy in colorectal tumors and showed minimal effects in melanoma. In this study, we developed an optimized bacterial strain producing a specific metabolite to broaden its therapeutic impact. Using flow cytometry, we assessed the effects of this enhanced strain on CTL activation and TME modulation across multiple cancer models. The optimized strain significantly increased inflammatory cytokine production, granzyme B expression, and CTL cytotoxicity within the TME. Notably, it reprogrammed the TME in melanoma models, leading to improved antitumor responses. These findings highlight the potential of our engineered bacteria to activate CTL-mediated immunity in a range of TMEs, advancing microbial immunotherapy as a versatile approach for multiple cancer types. Funding Sources Supported by NIH/NCI grant #1R01CA273002. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)