Pan-cancer analyses reveal cancer-type-specific fungal ecologies and bacteriome interactions

Cancer-microbe associations have been explored for centuries, but cancer-associated fungi have rarely been examined. Here, we comprehensively characterize the cancer mycobiome within 17,401 patient tissue, blood, and plasma samples across 35 cancer types in four independent cohorts. We report fungal DNA and cells at low abundances across many major human cancers, with differences in community compositions that differ among cancer types, even when accounting for technical background. Fungal histological staining of tissue microarrays supported intratumoral presence and frequent spatial association with cancer cells and macrophages. Comparing intratumoral fungal communities with matched bacteriomes and immunomes re-vealed co-occurring bi-domain ecologies, often with permissive, rather than competitive, microenvironments and distinct immune responses. Clinically focused assessments suggested prognostic and diagnostic ca-pacities of the tissue and plasma mycobiomes, even in stage I cancers, and synergistic predictive perfor-mance with bacteriomes.

Automated summary

This study comprehensively characterizes the cancer mycobiome in cancer patients and finds low abundances of fungi in various human cancers. The composition of fungal communities differs among cancer types and they are frequently associated with cancer cells and macrophages spatially. Comparisons with bacterial and immune communities reveal co-occurring bi-domain ecologies and distinct immune responses. The tissue and plasma mycobiomes show prognostic and diagnostic capabilities even in early stage cancers, and synergistic predictive performance with bacterial communities.