In:
PLOS Computational Biology, Public Library of Science (PLoS), Vol. 18, No. 12 ( 2022-12-22), p. e1010761-
Abstract:
Cells within a tumor microenvironment (TME) dynamically communicate and influence each other’s cellular states through an intercellular communication network (ICN). In cancers, intercellular communications underlie immune evasion mechanisms of individual tumors. We developed an individualized causal analysis framework for discovering tumor specific ICNs. Using head and neck squamous cell carcinoma (HNSCC) tumors as a testbed, we first mined single-cell RNA-sequencing data to discover gene expression modules (GEMs) that reflect the states of transcriptomic processes within tumor and stromal single cells. By deconvoluting bulk transcriptomes of HNSCC tumors profiled by The Cancer Genome Atlas (TCGA), we estimated the activation states of these transcriptomic processes in individual tumors. Finally, we applied individualized causal network learning to discover an ICN within each tumor. Our results show that cellular states of cells in TMEs are coordinated through ICNs that enable multi-way communications among epithelial, fibroblast, endothelial, and immune cells. Further analyses of individual ICNs revealed structural patterns that were shared across subsets of tumors, leading to the discovery of 4 different subtypes of networks that underlie disparate TMEs of HNSCC. Patients with distinct TMEs exhibited significantly different clinical outcomes. Our results show that the capability of estimating individual ICNs reveals heterogeneity of ICNs and sheds light on the importance of intercellular communication in impacting disease development and progression.
Type of Medium:
Online Resource
ISSN:
1553-7358
DOI:
10.1371/journal.pcbi.1010761
DOI:
10.1371/journal.pcbi.1010761.g001
DOI:
10.1371/journal.pcbi.1010761.g002
DOI:
10.1371/journal.pcbi.1010761.g003
DOI:
10.1371/journal.pcbi.1010761.g004
DOI:
10.1371/journal.pcbi.1010761.g005
DOI:
10.1371/journal.pcbi.1010761.g006
DOI:
10.1371/journal.pcbi.1010761.g007
DOI:
10.1371/journal.pcbi.1010761.g008
DOI:
10.1371/journal.pcbi.1010761.g009
DOI:
10.1371/journal.pcbi.1010761.g010
DOI:
10.1371/journal.pcbi.1010761.g011
DOI:
10.1371/journal.pcbi.1010761.t001
DOI:
10.1371/journal.pcbi.1010761.t002
DOI:
10.1371/journal.pcbi.1010761.s001
DOI:
10.1371/journal.pcbi.1010761.s002
DOI:
10.1371/journal.pcbi.1010761.s003
DOI:
10.1371/journal.pcbi.1010761.s004
DOI:
10.1371/journal.pcbi.1010761.s005
DOI:
10.1371/journal.pcbi.1010761.s006
DOI:
10.1371/journal.pcbi.1010761.s007
DOI:
10.1371/journal.pcbi.1010761.s008
DOI:
10.1371/journal.pcbi.1010761.s009
DOI:
10.1371/journal.pcbi.1010761.s010
DOI:
10.1371/journal.pcbi.1010761.s011
DOI:
10.1371/journal.pcbi.1010761.s012
DOI:
10.1371/journal.pcbi.1010761.s013
DOI:
10.1371/journal.pcbi.1010761.s014
DOI:
10.1371/journal.pcbi.1010761.s015
DOI:
10.1371/journal.pcbi.1010761.s016
DOI:
10.1371/journal.pcbi.1010761.s017
DOI:
10.1371/journal.pcbi.1010761.s018
DOI:
10.1371/journal.pcbi.1010761.s019
DOI:
10.1371/journal.pcbi.1010761.s020
DOI:
10.1371/journal.pcbi.1010761.r001
DOI:
10.1371/journal.pcbi.1010761.r002
DOI:
10.1371/journal.pcbi.1010761.r003
DOI:
10.1371/journal.pcbi.1010761.r004
DOI:
10.1371/journal.pcbi.1010761.r005
DOI:
10.1371/journal.pcbi.1010761.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2193340-6
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