{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T19:12:51Z","timestamp":1776193971859,"version":"3.50.1"},"reference-count":43,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2017YFC1201200"],"award-info":[{"award-number":["2017YFC1201200"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31671375"],"award-info":[{"award-number":["31671375"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31871339"],"award-info":[{"award-number":["31871339"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Cancer immune responses are complex cellular processes in which cytokine\u2013receptor interactions play central roles in cancer development and response to therapy; dysregulated cytokine\u2013receptor communication may lead to pathological processes, including cancer, autoimmune diseases, and cytokine storm; however, our knowledge regarding cytokine-mediated cell\u2013cell communication (CCI) in different cancers remains limited. The present study presents a single-cell and pan-cancer-level transcriptomics integration of 41,900 cells across 25 cancer types. We developed a single-cell method to actively express 62 cytokine\u2013receptor pairs to reveal stable cytokine-mediated cell communications involving 84 cytokines and receptors. The correlation between the sample-based CCI profile and the interactome analysis indicates multiple cytokine\u2013receptor modules including <jats:italic>TGFB1<\/jats:italic>, <jats:italic>IL16ST<\/jats:italic>, <jats:italic>IL15<\/jats:italic>, and the <jats:italic>PDGF<\/jats:italic> family. Some isolated cytokine interactions, such as <jats:italic>FN1<\/jats:italic>\u2013<jats:italic>IL17RC<\/jats:italic>, displayed diverse functions within over ten single-cell transcriptomics datasets. Further functional enrichment analysis revealed that the constructed cytokine\u2013receptor interaction map is associated with the positive regulation of multiple immune response pathways. Using public TCGA pan-cancer mutational data, co-mutational analysis of the cytokines and receptors provided significant co-occurrence features, implying the existence of cooperative mechanisms. Analysis of 10,967 samples from 32 TCGA cancer types revealed that the 84 cytokine and receptor genes are significantly associated with clinical survival time. Interestingly, the tumor samples with mutations in any of the 84 cytokines and receptors have a substantially higher mutational burden, offering insights into antitumor immune regulation and response. Clinical cancer stage information revealed that tumor samples with mutations in any of the 84 cytokines and receptors stratify into earlier tumor stages, with unique cellular compositions and clinical outcomes. This study provides a comprehensive cytokine\u2013receptor atlas of the cellular architecture in multiple cancers at the single-cell level.<\/jats:p>","DOI":"10.7717\/peerj.16221","type":"journal-article","created":{"date-parts":[[2023,12,2]],"date-time":"2023-12-02T07:17:06Z","timestamp":1701501426000},"page":"e16221","source":"Crossref","is-referenced-by-count":4,"title":["Identification of cytokine-induced cell communications by pan-cancer meta-analysis"],"prefix":"10.7717","volume":"11","author":[{"given":"Yining","family":"Liu","sequence":"first","affiliation":[{"name":"The School of Public Health, Institute for Chemical Carcinogenesis, Guangzhou Medical University,  Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Science and Engineering, University of the Sunshine Coast, Maroochydore DC, 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