The role of intestinal flora on tumorigenesis, progression, and the efficacy of PD-1/PD-L1 antibodies in colorectal cancer

Abstract

Intestinal flora affects the maturation of the host immune system, serves as a biomarker and efficacy predictor in the immunotherapy of several cancers, and has an important role in the development of colorectal cancer (CRC). Anti-PD-1/PD-L1 antibodies have shown satisfactory results in MSI-H/dMMR CRC but performed poorly in patients with MSS/pMMR CRC. In recent years an increasing number of studies have shown that intestinal flora has an important impact on anti-PD-1/PD-L1 antibody efficacy in CRC patients. Preclinical and clinical evidence have suggested that anti-PD-1/PD-L1 antibody efficacy can be improved by altering the composition of the intestinal flora in CRC. Herein, we summarize the studies related to the influence of intestinal flora on anti-PD-1/PD-L1 antibody efficacy in CRC and discuss the potential underlying mechanism(s). We have focused on the impact of the intestinal flora on the efficacy and safety of anti-PD-1/PD-L1 antibodies in CRC and how to better utilize the intestinal flora as an adjuvant to improve the efficacy of anti-PD-1/PD-L1 antibodies. In addition, we have provided a basis for the potential of the intestinal flora as a new treatment modality and indicator for determining patient prognosis.

Keywords: CD8⁺ T cell; Intestinal flora; anti-PD-1/PD-L1 therapy; colorectal cancer; immune checkpoint inhibitor.