The role of microbiome in CAR-T cell therapy

Chimeric Antigen Receptor (CAR) T-cell therapy represents a significant advancement in treating hematologic malignancies. However, its therapeutic efficacy against solid tumors remains hindered by several challenges, including suboptimal antitumor activity, high toxicity, and the emergence of resistance mechanisms. In recent years, the microbiome has emerged as a critical modulator of cancer immunotherapy outcomes. Yet, the precise molecular and cellular pathways through which the microbiome influences CAR-T cell efficacy remain largely unexplored. This chapter provides a comprehensive review of current knowledge regarding the interactions between CAR-T cell therapy and the microbiome, with particular emphasis on gut microbial dynamics. Additionally, it underscores the existing gaps in our understanding of these interactions and highlights key preclinical and clinical findings. We also discuss innovative strategies aimed at manipulating the microbiome to enhance CAR-T cell function, thereby presenting potential avenues for optimizing therapeutic outcomes.