MODULATING the gut microbiome may enhance immunotherapy responses in patients with solid tumors, according to a recent review exploring emerging evidence across melanoma, renal cell carcinoma (RCC), and non-small cell lung cancer (NSCLC). Specific bacterial species appear to play a crucial role in shaping host immunity and influencing therapeutic outcomes.
Preclinical and early clinical studies have identified Ruminococcaceae, Akkermansia, and Bifidobacterium as bacterial taxa associated with improved responses to immune checkpoint inhibitors (ICIs). Conversely, the use of antibiotics before or during ICI therapy has been linked to increased resistance and poorer survival, highlighting the microbiome’s vulnerability to disruption.
In an effort to personalize treatment, investigators have developed biomarkers such as TOPOSCORE to help predict immune response and quantify dysbiosis. These tools may provide future pathways to stratify patients and optimize therapy selection.
Several microbiome-focused interventions are under evaluation. Diet appears to play a role, with high fiber intake potentially correlating with better outcomes. Early trials also suggest that certain probiotics may enhance ICI efficacy when integrated into standard regimens. Another promising approach is fecal microbiota transplantation (FMT), which has demonstrated safety and signs of clinical benefit in ICI-refractory melanoma and in previously untreated patients with melanoma, RCC, or NSCLC.
Despite encouraging signals, the field is still in early stages. Most data come from small trials or observational studies, and definitive randomized evidence remains limited. The review emphasizes that large-scale trials will be essential before microbiome-targeted interventions can be incorporated into routine clinical practice.
The growing body of evidence linking gut health to immunotherapy response presents a compelling new frontier in oncology. As the mechanisms between microbiota and host immunity are further unraveled, future strategies may include targeted microbial manipulation as an adjunct to standard cancer therapies.
Reference:
Barragan-Carrillo R et al. Microbiome Modulation for the Treatment of Solid Neoplasms. J Clin Oncol. 2025:JCO2500374.
