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The tumour-associated microbiome

Nature Reviews Gastroenterology & Hepatology volume 19, pages 347–348 (2022)Cite this article

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The burgeoning field of intratumoural microbiome research has been driven by advances in next-generation sequencing technologies, with compelling evidence on the role of the microbiota in cancer initiation, progression and patient response to treatment. Here, we discuss new concepts of the tumour-associated microbiota and what is needed to advance the translational impact of these findings in gastrointestinal cancers.

The molecular evidence on the intratumoural microbiota of human cancers is compelling, but where do these microorganisms physically reside within tumours and what might this aspect tell us about their contribution to the tumour microenvironment? Application of targeted imaging approaches has demonstrated that these bacterial communities are tissue-invasive and exhibit intracellular lifestyles in epithelial and immune cell populations2,3. Strikingly, intraepithelial bacteria were shown to shape epitope presentation on cancer cells and potentially modulate immune cell activity in metastatic melanoma5. Unbiased approaches that can identify these intracellular bacteria and reveal the specific host cell types they interact with would meaningfully expand these findings, and help to evaluate the consequence of such interactions on host cellular functions within the tumour microenvironment. We expect that the adaptation and application of single-cell RNA sequencing approaches to simultaneously detect bacterial and host RNA from infected cells will be vital here. In addition, the presence of bacterial biofilms has been demonstrated to contribute to tumorigenesis in hereditary cancers at mucosal sites such as the colorectum6. We foresee that the coupling of targeted bacterial imaging approaches with spatial transcriptomics and spatial proteomic technologies will be fundamental to advancing our understanding of bacteria-colonized microniches, as they enable the analysis of host mRNA and proteins within tumour tissues in situ. The continuous exposure of gastrointestinal tract tumours to fairly high bacterial loads also warrants investigations into the modulation of immune cell migration and/or activity by the local microbiota and its influence on immunotherapies. Overall, the true contribution of the intratumoural microbiota to tumour cellular heterogeneity and the effect on cancer progression and patient response to treatment remains to be revealed.

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Fig. 1: The tumour-associated microbiota.

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Acknowledgements

C.D.J. is supported by the National Institute of Dental and Craniofacial Research of the NIH under award number R01 DE027850 and S.B. is supported by the National Cancer Institute (NCI) under award number R00 CA229984-03.

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Authors and Affiliations

  1. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Christopher D. Johnston

  2. Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Susan Bullman

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  1. Christopher D. Johnston
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  2. Susan Bullman
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Correspondence to Susan Bullman.

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Competing interests

C.D.J. has consulted for Seres Therapeutics and Azitra. S.B. has consulted for GlaxoSmithKline and BioMx; and is on the cancer programme advisory board for BioMx.

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Johnston, C.D., Bullman, S. The tumour-associated microbiome. Nat Rev Gastroenterol Hepatol 19, 347–348 (2022). https://doi.org/10.1038/s41575-022-00609-7

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