Gut microbiota: A double-edged sword in immune checkpoint blockade immunotherapy against tumors

Abstract

Tumor cells can evade immune surveillance by expressing immune checkpoint molecule ligands, resulting in effective immune cell inactivation. Immune checkpoint blockades (ICBs) have dramatically improved survival of patients with multiple types of cancers. However, responses to ICB immunotherapy are heterogeneous with lower patient response rates. The advances have established that the gut microbiota can be as a promising target to overcome resistance to ICB immunotherapy. Furthermore, some bacterial species have shown to promote improved responses to ICBs. However, gut microbiota is critical in maintaining gut and systemic immune homeostasis. It not only promotes differentiation and function of immunosuppressive immune cells but also inhibits inflammatory cells via gut microbiota derived products such as short chain fatty acids (SCFAs), tryptophan (Trp) and bile acid (BA) metabolites, which play an important role in tumor immunity. Since the gut microbiota can either inhibit or enhance immune against tumor, it should be a double-edged sword in ICBs against tumor. In this review, we discuss the effects of gut microbiota on immune cells and also tumor cells, especially enhances of gut microbiota on ICB immunotherapy. These discussions can hopefully promote the development of ICB immunotherapy.