Microbial metabolites for cancer immunotherapy: Current evidence and future directions

Abstract

Immune checkpoint blockade (ICB) therapy has transformed cancer treatment by activating the body's immune defenses to combat malignancies, offering substantial therapeutic outcomes for patients with advanced cancers. However, its efficacy varies considerably across different tumor types and individual patients. Recent studies have identified the human microbiome as a pivotal regulator of host homeostasis and systemic immunity and also found that it is essential for regulating immunotherapy's efficacy. Beyond direct microbial-host interactions, microbiota-derived immunomodulatory products, including metabolites, extracellular vesicles, and polysaccharides, have been shown to profoundly influence tumorigenesis, disease progression, and therapeutic responses. These microbial-derived immunomodulatory products can reshape the tumor microenvironment (TME) and modulate tumor immunity. Notably, emerging therapeutic strategies targeting or utilizing microbial immunomodulators have demonstrated promising efficacy in both preclinical and clinical models. This review provides a comprehensive overview of current research on microbiota-derived immunomodulatory products in cancer immunotherapy, highlighting their mechanistic roles and potential as innovative adjuncts in future tumor treatment strategies.

Keywords: BEVs; Bile acids; Immunotherapy; Metabolites; Microbiota; SCFAs; Tryptophan.