Pan-cancer analyses reveal cancer-type-specific fungal ecologies and bacteriome interactions

Lian Narunsky-Haziza; Gregory D Sepich-Poore; Ilana Livyatan; Omer Asraf; Cameron Martino; Deborah Nejman; Nancy Gavert; Jason E Stajich; Guy Amit; Antonio González; Stephen Wandro; Gili Perry; Ruthie Ariel; Arnon Meltser; Justin P Shaffer; Qiyun Zhu; Nora Balint-Lahat; Iris Barshack; Maya Dadiani; Einav N Gal-Yam; Sandip Pravin Patel; Amir Bashan; Austin D Swafford; Yitzhak Pilpel; Rob Knight; Ravid Straussman

doi:10.1016/j.cell.2022.09.005

Pan-cancer analyses reveal cancer-type-specific fungal ecologies and bacteriome interactions

Cell. 2022 Sep 29;185(20):3789-3806.e17. doi: 10.1016/j.cell.2022.09.005.

Authors

Lian Narunsky-Haziza¹, Gregory D Sepich-Poore², Ilana Livyatan³, Omer Asraf⁴, Cameron Martino⁵, Deborah Nejman⁶, Nancy Gavert⁶, Jason E Stajich⁷, Guy Amit⁸, Antonio González⁹, Stephen Wandro¹⁰, Gili Perry¹¹, Ruthie Ariel⁶, Arnon Meltser⁶, Justin P Shaffer⁹, Qiyun Zhu¹², Nora Balint-Lahat¹³, Iris Barshack¹³, Maya Dadiani¹⁴, Einav N Gal-Yam¹⁵, Sandip Pravin Patel¹⁶, Amir Bashan¹⁷, Austin D Swafford¹⁸, Yitzhak Pilpel⁴, Rob Knight¹⁹, Ravid Straussman²⁰

Affiliations

¹ Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
² Department of Bioengineering, University of California San Diego, La Jolla, CA, USA; Micronoma Inc., San Diego, CA, USA.
³ Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel; Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel.
⁴ Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
⁵ Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA, USA; Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA; Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA, USA.
⁶ Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
⁷ Department of Microbiology and Plant Pathology, Institute for Integrative Genome Biology, University of California Riverside, Riverside, CA, USA.
⁸ Department of Physics, Bar-Ilan University, Ramat-Gan, Israel; Department of Natural Sciences, The Open University of Israel, Raanana, Israel.
⁹ Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA, USA.
¹⁰ Micronoma Inc., San Diego, CA, USA.
¹¹ Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel; Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
¹² School of Life Sciences, Arizona State University, Tempe, AZ, USA; Biodesign Center for Fundamental and Applied Microbiomics, Arizona State University, Tempe, AZ, USA.
¹³ Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Department of Pathology, Sheba Medical Center, Ramat Gan, Israel.
¹⁴ Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel.
¹⁵ Breast Oncology Institute, Sheba Medical Center, Ramat Gan, Israel.
¹⁶ Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA; Moores Cancer Center, University of California San Diego Health, La Jolla, CA, USA.
¹⁷ Department of Physics, Bar-Ilan University, Ramat-Gan, Israel.
¹⁸ Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA.
¹⁹ Department of Bioengineering, University of California San Diego, La Jolla, CA, USA; Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA; Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA, USA; Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA. Electronic address: [email protected].
²⁰ Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. Electronic address: [email protected].

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

DNA, Fungal / analysis
Fungi / genetics
Humans
Mycobiome*
Neoplasms*

Substances

DNA, Fungal

Abstract

Publication types

MeSH terms

Substances

Grants and funding