Intestinal fungal signatures and their impact on immune checkpoint inhibitor efficacy: a multi-cohort meta-analysis

Gut microbiota influence on the effectiveness of immune checkpoint inhibitors (ICIs), but research on fungi-an essential component of the microbiome-has been limited. This multi-cohort meta-analysis of 976 fecal metagenomes across 8 cohorts, representing melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC), identified fungal species associated with ICI efficacy. In melanoma, Rhizophagus irregularis and Debaryomyces hansenii were correlated with poor responses, whereas Aspergillus avenaceus was associated with great efficacy. In NSCLC, an increased abundance of Aspergillus pseudonomiae was associated with a favorable prognosis. Stronger bacterial-fungal interactions were observed in responders. The presence of certain fungi in fungal enterotypes, like Aspergillus or Saccharomyces, was linked to better efficacy to ICIs. Mouse models revealed Debaryomyces hansenii impaired ICI efficacy by reducing CD8+ T cells. Our findings highlight specific fungal signatures that may inform strategies to enhance ICI efficacy and encourage further research on microbial impacts on treatment outcomes.