Immunometabolism: The role of gut-derived microbial metabolites in optimising immune response during checkpoint inhibitor therapy

Checkpoint inhibitor therapy is the most common type of immunotherapy used in the clinical setting, however, there are significant obstacles with treatment resistance and cancer progression. Since its introduction, there have been relatively few advances in the development of prognostic or predictive biomarkers. The field of metabolomics studies small molecules and can provide us with an understanding of the dynamic events evolving during the tumour-drug-immune-system interaction. Several key pathways have emerged as important in understanding resistance mechanisms thereby providing a rationale for targeting immunometabolism in order to enhance the immune response during checkpoint inhibitor therapy. In the first part of this review, we explore the role of gut microbiome-derived short-chain fatty acids, which are recognized as important immunoregulatory molecules shaping T-cell activation, effector and memory function. We then discuss tryptophan catabolism as a key predictor of primary checkpoint inhibitor failure. Lastly, we focus on immunometabolism as an important future target in immunotherapy. ONE SENTENCE SUMMARY: This review focusses on microbiome-derived metabolites and their role in immunometabolism and the enhancement of checkpoint inhibitor responses.