Targeted modulation of gut and intra-tumor microbiota to improve the quality of immune checkpoint inhibitor responses

Abstract

Immune checkpoint inhibitor (ICI) therapies, such as those blocking the interaction of PD-1 with its ligands, can restore the immune-killing function of T cells. However, ICI therapy is clinically beneficial in only a small number of patients, and it is difficult to predict post-treatment outcomes, thereby limiting its widespread clinical use. Research suggests that gut microbiota can regulate the host immune system and affect cancer progression and treatment. Moreover, the effectiveness of immunotherapy is related to the composition of the patient's gut microbiota; different gut microbial strains can either activate or inhibit the immune response. However, the importance of the microbial composition within the tumor has not been explored until recently. This study describes recent advances in the crosstalk between microbes in tumors and gut microbiota, which can modulate the tumor microbiome by directly translocating into the tumor and altering the tumor microenvironment. This study focused on the potential manipulation of the tumor and gut microbiota using fecal microbiota transplantation (FMT), probiotics, antimicrobials, prebiotics, and postbiotics to enrich immune-boosting bacteria while decreasing unfavorable bacteria to proactively improve the efficacy of ICI treatments. In addition, the use of genetic technologies and nanomaterials to modify microorganisms can largely optimize tumor immunotherapy and advance personalized and precise cancer treatment.

Keywords: Fecal microbiota transplantation; Gut microbiota; Immunotherapy; PD-1/PD-L1; Tumor microenvironment.