Intratumoral microbiota remodeling of the tumor microenvironment impact solid tumor immunotherapy

Abstract

Abstract Tumor immunotherapy has significantly advanced in recent years. However, few patients with solid tumors respond to immunotherapy. The tumor microenvironment (TME) is a key factor in immunotherapy efficacy, and the intratumoral microbiota plays a significant role in remodeling the TME. Recent multiomic analyses revealed bacterial signatures in up to 76% of pancreatic ductal adenocarcinoma (PDAC) cases, and specific microbial consortia were linked to therapeutic resistance. Microbiota-targeted therapies, such as engineered bacterial strains, increase tumor clearance rates by approximately 30% in preclinical models. However, the complexity of microbial mechanisms and heterogeneity among individuals limit the clinical translation of intratumoral microbiota-based therapies. In this review, we provide an overview of intratumoral microorganisms, explore their influence on immune cells and signaling pathways in the TME, and discuss their potential value for improving the response of solid tumors to immunotherapy. Specifically, we examine the unique characteristics of intratumoral microbes in different types of solid tumors, emphasizing how tumor microsatellite status plays a key role in determining the effects of intratumoral microbes on the response of solid tumors to immunotherapy. Additionally, we discuss the clinical application of the intratumoral microbiota as a potential method for improving treatment efficacy and prognosis prediction in patients receiving immunotherapy for solid tumors.