Jessica Jeong, Kelly J. Baines, Saman Maleki Vareki
The gut microbiome has emerged as a modulator of both cancer progression and patient responses to therapies like immune checkpoint inhibitors (ICI). Recent evidence highlights microbially derived metabolites as key regulators of immune response and tumor microenvironment dynamics. This review explores the role of four prominent classes of bacterial metabolites-inosine, indole, bile acids, and short-chain fatty acids-in shaping antitumor immunity and modulating ICI efficacy. Each of these metabolites and their derivatives demonstrate complex and context-dependent effects on immune cells. The duality of exerting both pro- and anti-inflammatory effects underscores the therapeutic potential and challenges of metabolite-targeted interventions. By examining current preclinical findings and ongoing clinical trials, we identify promising avenues for enhancing immunotherapy through microbiome modulation and call for further mechanistic insights to inform precision treatment strategies.