Decoding the microbiome-immune crosstalk in cancer: from mechanisms to therapeutic translation

The gut microbiome plays a critical role in shaping host immunity and profoundly affects the efficacy of cancer immunotherapy. Accumulating evidence suggests that interventions designed to alter the microbial community, including fecal microbiota transplantation, probiotics, and engineered bacteria, can reprogram the tumor-immune microenvironment and enhance clinical efficacy. This Review provides a comprehensive overview of the molecular and cellular mechanisms through which the gut microbiota influences antitumor immunity, and it highlights recent clinical studies evaluating these interventions. We further examine inherent challenges, including inter-individual variability in microbial composition, difficulties in achieving stable and durable colonization, technical barriers in delivery, and potential safety concerns associated with immune activation or off-target effects. Finally, we discuss future directions for translating microbiome-targeted therapies into oncology, emphasizing the need for mechanistic insight, standardized protocols, rigorous evaluation, and integration with precision immunotherapy strategies to optimize therapeutic outcomes.