Tumor Microenvironment Targeted by Polysaccharides in Cancer Prevention: Expanding Roles of Gut Microbiota and Metabolites

ABSTRACT Since the development of immune checkpoint inhibitors (ICIs), immunotherapy has been widely used as a novel cancer treatment. However, the efficacy of tumor immunotherapy is largely dependent on the tumor microenvironment (TME). The high degree of heterogeneity within TME remains a major obstacle to acquire satisfactory therapeutic. Emerging studies suggest that gut microbiota is becoming an important regulator of TME. Polysaccharides as tumor immunotherapeutic agents or immune adjuvants not only exhibit antitumor activity by targeting gut microbiota, but also expand their role in the tumor immunotherapy by remodeling TME. To date, the mechanism by which polysaccharides targeting TME for tumor prevention via gut microbiota has not been deeply investigated. In this review, recent advances in the regulation of TME by polysaccharides through gut microbiota were systematically outlined, and the challenges and possible solutions in the clinical application of TME‐targeted polysaccharides were discussed. Exploring the relationship between polysaccharides and TME from the perspective of gut microbiota may provide new ideas for the application of polysaccharides in tumor immunotherapy. This is a new area with major challenges that deserve further exploration.