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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\u2010drug\u2010immune\u2010system 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\u2010derived short\u2010chain fatty acids, which are recognized as important immunoregulatory molecules shaping T\u2010cell 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>One sentence summary<\/jats:title><jats:p>This review focusses on microbiome\u2010derived metabolites and their role in immunometabolism and the enhancement of checkpoint inhibitor responses.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.70472","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T09:47:52Z","timestamp":1757065672000},"source":"Crossref","is-referenced-by-count":8,"title":["Immunometabolism: The role of gut\u2010derived microbial metabolites in optimising immune response during checkpoint inhibitor therapy"],"prefix":"10.1002","volume":"15","author":[{"given":"Agnieszka Beata","family":"Malczewski","sequence":"first","affiliation":[{"name":"Icon Cancer Centre, Wesley and South Brisbane  Brisbane Queensland Australia"},{"name":"Faculty of Medicine University of Queensland  Brisbane Queensland 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