Emerging roles of the gut microbiota in cancer immunotherapy

Abstract

Gut microbiota represents a hidden treasure vault encompassing trillions of microorganisms that inhabit the intestinal epithelial barrier of the host. In the past decade, numerous in-vitro, animal and clinical studies have revealed the profound roles of gut microbiota in maintaining the homeostasis of various physiological functions, especially immune modulation, and remarkable differences in the configuration of microbial communities between cancers and healthy individuals. In addition, although considerable efforts have been devoted to cancer treatments, there remain many patients succumb to their disease with the incremental cancer burden worldwide. Nevertheless, compared with the stability of human genome, the plasticity of gut microbiota renders it a promising opportunity for individualized treatment. Meanwhile, burgeoning findings indicate that gut microbiota is involved in close interactions with the outcomes of diverse cancer immunotherapy protocols, including immune checkpoint blockade therapy, allogeneic hematopoietic stem cell transplantation, and chimeric antigen receptor T cell therapy. Here, we reviewed the evidence for the capacity of gut microflora to modulate cancer immunotherapies, and highlighted the opportunities of microbiota-based prognostic prediction, as well as microbiotherapy by targeting the microflora to potentiate anticancer efficacy while attenuating toxicity, which will be pivotal to the development of personalized cancer treatment strategies.

Keywords: Gut microbiota; allogeneic hematopoietic stem cell transplantation; chimeric antigen receptor T cell therapy; immune checkpoint blockade; immunotherapy.

Figure 1

Interactions between the gut microbiota and cancer immunotherapy. The intestinal microbial ecosystem can be well modified by multiple patterns, including diets, drugs, prebiotics, probiotics, and FMT, which provide fascinating opportunities for the clinical managements of diverse cancer immunotherapy protocols such as ICB therapy, allo-HSCT, and CAR-T cell therapy. FMT, fecal microbiota transplantation; ICB, immune checkpoint blockade; allo-HSCT, allogeneic hematopoietic stem cell transplantation; CAR-T, chimeric antigen receptor T. (By Figdraw).

Figure 2

The underlying molecular mechanisms on the gut microbiota-derived metabolites that mediated the responses of ICB therapy. SCFAs, short−chain fatty acids; TMAO, trimethylamine N-oxide; IECs, intestinal epithelial cells; ICB, immune checkpoint blockade; TAM, tumor-associated macrophage; TME, tumor microenvironment. (By Figdraw).