Graphical Abstract
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.
Authors
LianNarunsky-Haziza1,2,20, Gregory D. Sepich-Poore3,11,20, Ilana Livyatan1,4,20, Omer Asraf2,21, Cameron Martino5,6,7,21, Deborah Nejman1, Nancy Gavert1, Jason E. Stajich8, Guy Amit9,10, Antonio González7, Stephen Wandro11, Gili Perry1, 12, 15, Ruthie Ariel1, Arnon Meltser1, Justin P. Shaffer7, Qiyun Zhu13,14, Nora Balint-Lahat15,16, Iris Barshack15,16, Maya Dadiani12, Einav N. Gal-Yam17, Sandip Pravin Patel6,18, Amir Bashan9, Austin D. Swafford6, Yitzhak Pilpel2,22, Rob Knight3,6,7,19,22, Ravid Straussman1,22,23
- 1 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
- 2Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
- 3Department of Bioengineering, University of California San Diego, La Jolla, CA, USA
- 4Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel
- 5Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA, USA
- 6Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
- 7Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA, USA
- 8Department of Microbiology and Plant Pathology, Institute for Integrative Genome Biology, University of California Riverside, Riverside, CA, USA
- 9Department of Physics, Bar-Ilan University, Ramat-Gan, Israel
- 10Department of Natural Sciences, The Open University of Israel, Raanana, Israel
- 11Micronoma Inc., San Diego, CA, USA
- 12Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel
- 13School of Life Sciences, Arizona State University, Tempe, AZ, USA
- 14Biodesign Center for Fundamental and Applied Microbiomics, Arizona State University, Tempe, AZ, USA
- 15Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- 16Department of Pathology, Sheba Medical Center, Ramat Gan, Israel
- 17Breast Oncology Institute, Sheba Medical Center, Ramat Gan, Israel
- 18 Moores Cancer Center, University of California San Diego Health, La Jolla, CA, USA
- 19 Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA