Pan-cancer analyses reveal cancer-type-specific fungal ecologies and bacteriome interactions
- PMID: 36179670
- PMCID: PMC9567272
- DOI: 10.1016/j.cell.2022.09.005
Pan-cancer analyses reveal cancer-type-specific fungal ecologies and bacteriome interactions
Abstract
Cancer-microbe associations have been explored for centuries, but cancer-associated fungi have rarely been examined. Here, we comprehensively characterize the cancer mycobiome within 17,401 patient tissue, blood, and plasma samples across 35 cancer types in four independent cohorts. We report fungal DNA and cells at low abundances across many major human cancers, with differences in community compositions that differ among cancer types, even when accounting for technical background. Fungal histological staining of tissue microarrays supported intratumoral presence and frequent spatial association with cancer cells and macrophages. Comparing intratumoral fungal communities with matched bacteriomes and immunomes revealed co-occurring bi-domain ecologies, often with permissive, rather than competitive, microenvironments and distinct immune responses. Clinically focused assessments suggested prognostic and diagnostic capacities of the tissue and plasma mycobiomes, even in stage I cancers, and synergistic predictive performance with bacteriomes.
Keywords: biomarkers; cancer; fungi; liquid biopsy; metagenomics; metatranscriptomics; microbial interactions; tumor microbiome; tumor mycobiome.
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of interests G.D.S.-P. and R.K. are inventors on a US patent application (PCT/US2019/059647) submitted by The Regents of the University of California and licensed by Micronoma; that application covers methods of diagnosing and treating cancer using multi-domain microbial biomarkers in blood and cancer tissues. G.D.S.-P. and R.K. are founders of and report stock interest in Micronoma. G.D.S.-P. has filed several additional US patent applications on cancer bacteriome and mycobiome diagnostics that are owned by The Regents of the University of California. R.K. additionally is a member of the scientific advisory board for GenCirq, holds an equity interest in GenCirq, and can receive reimbursements for expenses up to US $5,000 per year. S.W. is an employee of Micronoma. R.S. received a grant from Merck EMD Serono, is a member of the scientific advisory board for Micronoma and reports stock interest in Micronoma, CuResponse, and Biomica, and is a paid adviser to Biomica, CuResponse, and BiomX. R.S., Y.P., I.L., and L.N.-H. are co-inventors on an Israeli provisional patent application (#284860) submitted by Yeda Research and Development, the Weizmann Institute of Science, that covers methods of diagnosing and treating cancer using mycobial biomarkers in cancer tissues.
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Comment in
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The tumor mycobiome: A paradigm shift in cancer pathogenesis.Cell. 2022 Sep 29;185(20):3648-3651. doi: 10.1016/j.cell.2022.09.013. Cell. 2022. PMID: 36179665 Free PMC article.
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Fungi in cancer: not such a 'fun-guy'.Nat Rev Cancer. 2022 Dec;22(12):659. doi: 10.1038/s41568-022-00533-7. Nat Rev Cancer. 2022. PMID: 36323799 No abstract available.
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The fungal mycobiome: a new hallmark of cancer revealed by pan-cancer analyses.Signal Transduct Target Ther. 2023 Feb 1;8(1):50. doi: 10.1038/s41392-023-01334-6. Signal Transduct Target Ther. 2023. PMID: 36725834 Free PMC article. No abstract available.
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References
-
- Alam A., Levanduski E., Denz P., Villavicencio H.S., Bhatta M., Alhorebi L., Zhang Y., Gomez E.C., Morreale B., Senchanthisai S., et al. Fungal mycobiome drives IL-33 secretion and type 2 immunity in pancreatic cancer. Cancer Cell. 2022;40 doi: 10.1016/j.ccell.2022.01.003. 153.e11–167.e11. - DOI - PMC - PubMed
-
- Allaband C., Lingaraju A., Martino C., Russell B., Tripathi A., Poulsen O., Dantas Machado A.C., Zhou D., Xue J., Elijah E., et al. Intermittent hypoxia and hypercapnia alter diurnal rhythms of luminal gut microbiome and metabolome. mSystems. 2021:e0011621. doi: 10.1128/mSystems.00116-21. - DOI - PMC - PubMed
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