Gut microbiome in immuno-oncology: potential for clinical exploitation

Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape of multiple malignancies, yet durable clinical benefit remains limited to a subset of patients, while immune-related adverse events still represent a major therapeutic challenge. Over the past decade, compelling evidence has established the gut microbiota as a key host determinant of both the efficacy and toxicity of cancer immunotherapy. Given its profound diversity and plasticity, as well as its impact on systemic immunity, gut commensals are now considered as both a promising predictive biomarker of response and a potentially actionable therapeutic target. As a result, different microbiota-informed approaches are being explored for precision immune-oncology. Specifically, emerging biomarker strategies are moving beyond single bacterial taxa toward ecological and functional microbial signatures with improved reproducibility across patient cohorts. At the same time, therapeutic modulation of the gut microbiome, through dietary interventions, prebiotics, probiotics, and fecal microbiota transplantation, is being actively investigated to enhance responsiveness to ICIs and mitigate immune-related adverse events. In this review, we discuss the biological mechanisms linking gut microbiota and immunotherapy, evaluate its role as biomarker and therapeutic target, and address the current challenges that need to be overcome to integrate microbiota into precision immune-oncology.