Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer

• DOI: 10.1038/s41586-022-05435-0
• Publication Date: 2022-11-16T17:05:04Z
• Authors: Jorge Luis Galean...; Hanrui Wu; Kaitlyn D. LaCourse; Andrew G. Kempchi...; Alexander Baryiames; Brittany Barber; Neal Futran; Jeffrey Houlton; Cassie Sather; Ewa Sicinska; Alison Taylor; Samuel S. Minot; Christopher D. Jo...; Susan Bullman
• Keywords: Host Microbial Interactions; Sequence Analysis, RNA; Microbiota; Gene Expression Profiling; Article; 3. Good health; Ki-67 Antigen; Carcinoma, Squamous Cell; Tumor Microenvironment; Disease Progression; Humans; Mouth Neoplasms; Myeloid Cells; Colorectal Neoplasms

Abstract The tumour-associated microbiota is an intrinsic component of the tumour microenvironment across human cancer types 1,2 . Intratumoral host–microbiota studies have so far largely relied on bulk tissue analysis 1–3 , which obscures spatial distribution and localized effect within tumours. Here, by applying in situ spatial-profiling technologies 4 single-cell RNA sequencing 5 to oral squamous cell carcinoma colorectal cancer, we reveal spatial, cellular molecular host–microbe interactions. We adapted 10x Visium transcriptomics determine identity location intratumoral microbial communities patient tissues. Using GeoMx digital profiling 6 show that bacterial populate microniches are less vascularized, highly immuno‑suppressive associated with malignant cells lower levels Ki-67 as compared bacteria-negative regions. developed a RNA-sequencing method name INVADEseq (invasion–adhesion-directed expression sequencing) and, this tumours, identify cell-associated bacteria host they interact, well uncovering alterations transcriptional pathways involved inflammation, metastasis, dormancy DNA repair. Through functional studies, infected invade their surrounding environment single recruit myeloid Collectively, our data not random; instead, it organized immune epithelial functions promote progression.