Jorge Luis Galeano Niño; Hanrui Wu; Kaitlyn D. LaCourse; Andrew G. Kempchinsky; Alexander Baryiames; Brittany Barber; Neal D. Futran; Jeffrey Houlton; Cassie Sather; Ewa Sicińska; Alison Taylor; Samuel S. Minot; Christopher D. Johnston; Susan Bullman · 2022 · Nature
Paper
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 the spatial distribution and localized effect of the microbiota within tumours. Here, by applying in situ spatial-profiling technologies 4 and single-cell RNA sequencing 5 to oral squamous cell carcinoma and colorectal cancer, we reveal spatial, cellular and molecular host–microbe interactions. We adapted 10x Visium spatial transcriptomics to determine the identity and in situ location of intratumoral microbial communities within patient tissues. Using GeoMx digital spatial profiling 6, we show that bacterial communities populate microniches that are less vascularized, highly immuno‑suppressive and associated with malignant cells with lower levels of Ki-67 as compared to bacteria-negative tumour regions. We developed a single-cell RNA-sequencing method that we name INVADEseq (invasion–adhesion-directed expression sequencing) and, by applying this to patient tumours, identify cell-associated bacteria and the host cells with which they interact, as well as uncovering alterations in transcriptional pathways that are involved in inflammation, metastasis, cell dormancy and DNA repair. Through functional studies, we show that cancer cells that are infected with bacteria invade their surrounding environment as single cells and recruit myeloid cells to bacterial regions. Collectively, our data reveal that the distribution of the microbiota within a tumour is not random; instead, it is highly organized in microniches with immune and epithelial cell functions that promote cancer progression.
Analysis
This study reveals that the intratumoral microbiota is organized into specific microniches within tumors, influencing host cell functions and promoting cancer progression through altered transcriptional pathways and enhanced invasion.
Discovery
Jongsu Lim; Chanho Park; Minjae Kim; Hyukhee Kim; Junil Kim; Dong-Sung Lee
Kai Zhang; Nathan R. Zemke; Ethan J. Armand; Bing Ren
Cameron G. Williams; Hyun Jae Lee; Takahiro Asatsuma; Roser Vento‐Tormo; Ashraful Haque
Dragomirka Jovic; Xue Liang; Hua Zeng; Lin Lin; Fengping Xu; Yonglun Luo
Saket Choudhary; Rahul Satija
Malte D. Luecken; Maren Büttner; Kridsadakorn Chaichoompu; Anna Danese; Marta Interlandi; Martin Mueller; Daniel Strobl; Luke Zappia; Martin Dugas; Maria Colomé‐Tatché; Fabian J. Theis
Source record