Microbiome Signatures Predict Melanoma Recurrence After Adjuvant ICI Therapy

A recent study published in the journal Cell reveals that the gut microbiome can predict melanoma recurrence after adjuvant immune checkpoint blockade (ICB) treatment with up to 94% accuracy in certain patient subgroups, offering a potential biomarker to guide personalized therapy for high-risk melanoma patients.

Researchers analyzed stool samples from 674 patients enrolled in the phase 3 CheckMate 915 clinical trial, which compared nivolumab plus ipilimumab versus nivolumab alone across five geographic regions. The study aimed to determine whether pre-treatment gut microbiome features could predict recurrence in patients with resected, high-risk melanoma receiving adjuvant ICB, a setting where 25% to 40% of patients still experience recurrence despite treatment.

Using region-specific and cross-region meta-analyses, the team identified specific bacterial taxa associated with recurrence, including Eubacterium, Ruminococcus, Firmicutes, and Clostridium. The predictive power of these microbiome signatures was strongest when the validation cohort’s gut microbiome profile closely matched that of the discovery cohort, measured by a Jensen-Shannon divergence (JSD) of 0.11 or less.

Among these closely matched individuals, the area under the curve (AUC) for recurrence prediction ranged from 0.78 to 0.94 across different geographic regions, indicating strong discriminatory ability. An AUC of 0.94 corresponds to approximately 94% accuracy in distinguishing between patients who would and would not experience recurrence.

The study also found that gut microbiome composition remained largely stable following treatment, suggesting that pre-treatment microbial profiles could serve as reliable baseline biomarkers. These findings support the potential use of gut bacterial markers as clinically actionable tools to stratify recurrence risk and inform personalized therapeutic strategies in melanoma patients undergoing adjuvant immune checkpoint blockade.

Usyk M, Hayes RB, Knight R, Gonzalez A, Li H, Osman I, Weber JS, Ahn J. Gut microbiome is associated with recurrence-free survival in patients with resected Stage IIIB-D or Stage IV melanoma treated with immune checkpoint inhibitors. Cell. 2026.