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

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-YamSandip Pravin Patel, Amir Bashan, Austin D. Swafford, Yitzhak Pilpel, Rob Knight^*, Ravid Straussman^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

282 Scopus citations

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.

Original language	English
Pages (from-to)	3789-3806.e17
Journal	Cell
Volume	185
Issue number	20
DOIs	https://doi.org/10.1016/j.cell.2022.09.005
State	Published - 29 Sep 2022

Funding

Funders	Funder number
Dr. Dvora and Haim Teitelbaum Endowment Fund
Fabrikant-Morse Families Research Fund for Humanity
Israel Cancer Research Fund and City of Hope	HHSN261201500003I, HHSN261201400008C, 17X146, 5K12GM068524-17
Merck EMD Serono	284860
Moross Integrated Cancer Center
Swiss Society Institute for Cancer Prevention Research
National Institutes of Health	DP1AT010885
National Institute on Drug Abuse	P50DA026306
National Cancer Institute	F30 CA243480, U24 CA248454, R01 CA255206
University of California
Horizon 2020 Framework Programme
European Research Council
Weizmann Institute of Science
United States-Israel Binational Science Foundation	2013332
Israel Science Foundation	2927/21
Horizon 2020	818086
Rising Tide Foundation

Keywords

biomarkers
cancer
fungi
liquid biopsy
metagenomics
metatranscriptomics
microbial interactions
tumor microbiome
tumor mycobiome

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cell.2022.09.005

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Narunsky-Haziza, L., Sepich-Poore, G. D., Livyatan, I., Asraf, O., Martino, C., Nejman, D., Gavert, N., Stajich, J. E., Amit, G., González, A., Wandro, S., Perry, G., Ariel, R., Meltser, A., Shaffer, J. P., Zhu, Q., Balint-Lahat, N., Barshack, I., Dadiani, M., ... Straussman, R. (2022). Pan-cancer analyses reveal cancer-type-specific fungal ecologies and bacteriome interactions. Cell, 185(20), 3789-3806.e17. https://doi.org/10.1016/j.cell.2022.09.005

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title = "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",

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

note = "Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = sep,

day = "29",

doi = "10.1016/j.cell.2022.09.005",

language = "אנגלית",

volume = "185",

pages = "3789--3806.e17",

journal = "Cell",

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Narunsky-Haziza, L, Sepich-Poore, GD, Livyatan, I, Asraf, O, Martino, C, Nejman, D, Gavert, N, Stajich, JE, Amit, G, González, A, Wandro, S, Perry, G, Ariel, R, Meltser, A, Shaffer, JP, Zhu, Q, Balint-Lahat, N, Barshack, I, Dadiani, M, Gal-Yam, EN, Patel, SP, Bashan, A, Swafford, AD, Pilpel, Y, Knight, R & Straussman, R 2022, 'Pan-cancer analyses reveal cancer-type-specific fungal ecologies and bacteriome interactions', Cell, vol. 185, no. 20, pp. 3789-3806.e17. https://doi.org/10.1016/j.cell.2022.09.005

TY - JOUR

T1 - Pan-cancer analyses reveal cancer-type-specific fungal ecologies and bacteriome interactions

AU - Narunsky-Haziza, Lian

AU - Sepich-Poore, Gregory D.

AU - Livyatan, Ilana

AU - Asraf, Omer

AU - Martino, Cameron

AU - Nejman, Deborah

AU - Gavert, Nancy

AU - Stajich, Jason E.

AU - Amit, Guy

AU - González, Antonio

AU - Wandro, Stephen

AU - Perry, Gili

AU - Ariel, Ruthie

AU - Meltser, Arnon

AU - Shaffer, Justin P.

AU - Zhu, Qiyun

AU - Balint-Lahat, Nora

AU - Barshack, Iris

AU - Dadiani, Maya

AU - Gal-Yam, Einav N.

AU - Patel, Sandip Pravin

AU - Bashan, Amir

AU - Swafford, Austin D.

AU - Pilpel, Yitzhak

AU - Knight, Rob

AU - Straussman, Ravid

PY - 2022/9/29

Y1 - 2022/9/29

N2 - 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.

AB - 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.

KW - biomarkers

KW - cancer

KW - fungi

KW - liquid biopsy

KW - metagenomics

KW - metatranscriptomics

KW - microbial interactions

KW - tumor microbiome

KW - tumor mycobiome

UR - http://www.scopus.com/inward/record.url?scp=85138486612&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2022.09.005

DO - 10.1016/j.cell.2022.09.005

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 36179670

AN - SCOPUS:85138486612

SN - 0092-8674

VL - 185

SP - 3789-3806.e17

JO - Cell

JF - Cell

IS - 20

ER -

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

Abstract

Funding

Keywords

UN SDGs

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