Intratumoral Microbiome of Adenoid Cystic Carcinomas and Comparison with other Head and Neck Cancers

Abstract

ABSTRACTBackgroundAdenoid cystic carcinoma (ACC) is a rare, slow growing yet aggressive head and neck malignancy. Despite its clinical significance, our understanding of the cellular evolution and microenvironment in ACC remains limited.MethodsWe investigated the intratumoral microbiome of 50 ACC tumors and 33 adjacent normal tissues using 16S rRNA gene sequencing. This allowed us to characterize the bacterial communities within ACC and explore potential associations between the bacterial community structure, patient’s clinical characteristics, and tumor molecular features obtained through RNA sequencing.ResultsBacterial composition in ACC displayed significant differences compared to adjacent normal salivary tissue and exhibited diverse levels of species richness. We identified two main microbial subtypes within ACC: oral-like and gut-like. Oral-like microbiomes, characterized by higher diversity and abundance of genera likeNeisseria, Leptotrichia, Actinomyces, Streptococcus, Rothia, andVeillonella(commonly found in healthy oral cavities), were associated with the less aggressive ACC-II molecular subtype and improved patient outcomes. Notably, we identified the same oral genera in oral cancer and in head and neck squamous cell carcinomas. In both cancers, they were part of shared oral communities associated with more diverse microbiome, less aggressive tumor phenotype, and better survival. Conversely, gut-like microbiomes in ACC, featuring low diversity and colonization by gut mucus layer-degrading species likeBacteroides, Akkermansia, Blautia, Bifidobacterium, andEnterococcus, were associated with poorer outcomes. Elevated levels ofBacteroides thetaiotaomicronwere independently associated with significantly worse survival, regardless of other clinical and molecular factors. Furthermore, this association positively correlated with tumor cell biosynthesis of glycan-based cell membrane components.ConclusionsOur study uncovers specific intratumoral oral genera as potential pan-cancer biomarkers for favorable microbiomes in ACC and other head and neck cancers. These findings highlight the pivotal role of the intratumoral microbiome in influencing ACC prognosis and disease biology.