Manipulating the gut and tumor microbiota for immune checkpoint inhibitor therapy: from dream to reality.

The response of patients to immunotherapy can vary significantly due to differences in their gut and tumor microbiomes. Gut bacteria play a crucial role in shaping the host immune system, tumor immunity, and response to immunotherapy, which makes them key predictors and targets for immunotherapy. Bacteria can also colonize and persist within tumor cells, affecting cancer initiation, progression, metastasis, and treatment response. The specific gut and tumor composition of bacteria can robustly predict the clinical outcomes and adverse effects. Diet, prebiotics, probiotics, metabolites, and antibiotics that have an impact on the microbiome influence the response to immunotherapy. Manipulating the microbiome remains challenging as we lack a complete understanding of the modes of action of the tumor and gut microbiomes. The past decade has witnessed a revolution in cancer treatment by shifting from conventional therapies to immune checkpoint inhibitors (ICIs). These immunotherapies unleash the host immune system against the tumor and have achieved unprecedented durable remission. However, 80% of patients do not respond. This review discusses how bacteria are unexpected drivers that reprogram tumor immunity. Manipulating the microbiota impacts on tumor development and reprograms the tumor microenvironment (TME) of mice on immunotherapy. We anticipate that harnessing commensals and the tumor microbiome holds promise to identify patients who will benefit from immunotherapy and guide the choice of new ICI combinations to advance treatment efficacy. [ABSTRACT FROM AUTHOR]