The effect of the microbiota present within tumors on the cellular and spatial variability of cancer
The microbiota that lives in and around tumors is an important part of the microenvironment of all types of human cancer. So far, most studies of the relationship between the host and the microbiota inside a tumor have used bulk tissue analysis, which makes it hard to see how the microbiota are distributed and how they affect different parts of the tumor.
Researchers use spatial-profiling technologies and single-cell RNA sequencing on oral squamous cell carcinoma and colorectal cancer to find out how the host and microbes interact in space, at the level of individual cells, and at the molecular level. They adapted 10x Visium spatial transcriptomics to find out the identity of the intratumoral microbial communities and where they were in patient tissues. Using GeoMx digital spatial profiling, researchers show that bacterial communities live in micro niches that have less blood flow, are more immunosuppressive, and have malignant cells with lower Ki-67 levels than tumor regions without bacteria.
Researchers made a single-cell RNA-sequencing method that they call INVADEseq (invasion-adhesion-directed expression sequencing). When they used it on patient tumors, they found cell-associated bacteria and the host cells with which they interact. They also found changes in transcriptional pathways that are involved in inflammation, metastasis, cell dormancy, and DNA repair. They know that cancer cells that are infected with bacteria invade their surroundings as single cells and bring myeloid cells to areas where bacteria are.
Together, the research shows that the microbiota in a tumor is not spread out at random. Instead, it is highly organized into micro niches where immune and epithelial cells work in ways that help cancer spread.
Galeano Niño, J. L., Wu, H., LaCourse, K. D., Kempchinsky, A. G., Baryiames, A., Barber, B., Futran, N., Houlton, J., Sather, C., Sicinska, E., Taylor, A., Minot, S. S., Johnston, C. D., & Bullman, S. (2022). Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer. Nature, 10.1038/s41586-022-05435-0. Advance online publication. https://doi.org/10.1038/s41586-022-05435-0
ABSTRACT The human gut microbiota is considered one of the most fascinating reservoirs of microbial diversity hosting between 400 to 1000 bacterial species distributed among nine phyla with Firmicutes, Bacteroidetes and Actinobacteria representing around of the diversity. One of the most intriguing issues relates to understanding which microbial groups are active players in the maintenance … Continue reading
Abstract Hundreds of different species colonize multicellular organisms making them “meta organisms”. A growing body of data supports the role of microbiota in health and in disease. Grasping the principles of host-microbiota interactions (HMIs) at the molecular level is important since it may provide insights into the mechanisms of infections. The crosstalk between the host and … Continue reading