Microbiome interactions in renal cell carcinoma: evidence, challenges and opportunities

Renal cell carcinoma (RCC) is a heterogeneous malignancy with limited predictive biomarkers to guide treatment. Emerging evidence suggests that the microbiome might influence systemic immunity, therapeutic response and clinical outcomes. In metastatic RCC, the gut microbiome has been linked to the efficacy of immune checkpoint inhibitors, whereas the existence of a tumour microbiome remains a topic of debate. Circulating microbial DNA in blood has been proposed as a minimally invasive window into systemic immune status, offering a potential tool for monitoring treatment response, but its role in RCC is largely unexplored. Evidence from mechanistic studies, primarily from other solid cancer types, suggests that microbiome-immune crosstalk, microbial metabolites and functionally redundant pathways across taxa could modulate tumour biology. However, progress in RCC microbiome research remains limited by small cohorts, methodological variability and challenges in working with samples with a low microbial biomass, which are highly prone to contamination. Emerging spatial and multi-omics technologies now enable high-resolution mapping of these complex interactions, offering the potential to transform our understanding of the cancer microbiome. A structured roadmap is required to overcome technical and analytical challenges in RCC microbiome studies, enabling the identification of clinically relevant microbial signatures and their role in shaping tumour immunity.