CAR-T Cell Therapy and the Gut Microbiota

SIMPLE SUMMARY: CAR-T cell therapy has recently revolutionized the field of cancer therapeutics, especially for hematological malignancies, and is also evolving as an experimental therapeutic option for solid tumors. Despite the groundbreaking initial response rates, nearly half of CAR-T cell treated patients have a lower response rate and experience major adverse effects. Recently, the microbiota has been suggested to constitute a contributing factor possibly impacting host antitumor CAR-T cell-mediated immune responses. As such, microbiota signatures may be harnessed to personally predict therapy response or adverse effects in optimizing CAR-T therapy to the individual. Collectively, personalized diagnostic and therapeutic utilization of the microbiota holds vast potential in achieving a safer and more efficacious CAR-T cell-based treatment. ABSTRACT: Chimeric antigen receptor (CAR) - T cell cancer therapy has yielded promising results in treating hematologic malignancies in clinical studies, and a growing number of CAR-T regimens are approved for clinical usage. While the therapy is considered of great potential in expanding the cancer immunotherapy arsenal, more than half of patients receiving CAR-T infusions do not respond, while others develop significant adverse effects, collectively indicating a need for optimization of CAR-T treatment to the individual. The microbiota is increasingly suggested as a major modulator of immunotherapy responsiveness. Studying causal microbiota roles possibly contributing to CAR-T therapy efficacy, adverse effects reduction, and prediction of patient responsiveness constitutes an exciting area of active research. Herein, we discuss the latest developments implicating human microbiota involvement in CAR-T therapy, while highlighting challenges and promises in harnessing the microbiota as a predictor and modifier of CAR-T treatment towards optimized efficacy and minimization of treatment-related adverse effects.