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Article: Nasopharyngeal carcinoma cells promote regulatory T cell development and suppressive activity via CD70-CD27 interaction

TitleNasopharyngeal carcinoma cells promote regulatory T cell development and suppressive activity via CD70-CD27 interaction
Authors
Issue Date6-Apr-2023
PublisherNature Research
Citation
Nature Communications, 2023, v. 14, n. 1 How to Cite?
Abstract

Despite the intense CD8+ T-cell infiltration in the tumor microenvironment of nasopharyngeal carcinoma, anti-PD-1 immunotherapy shows an unsatisfactory response rate in clinical trials, hindered by immunosuppressive signals. To understand how microenvironmental characteristics alter immune homeostasis and limit immunotherapy efficacy in nasopharyngeal carcinoma, here we establish a multi-center single-cell cohort based on public data, containing 357,206 cells from 50 patient samples. We reveal that nasopharyngeal carcinoma cells enhance development and suppressive activity of regulatory T cells via CD70-CD27 interaction. CD70 blocking reverts Treg-mediated suppression and thus reinvigorate CD8+ T-cell immunity. Anti-CD70+ anti-PD-1 therapy is evaluated in xenograft-derived organoids and humanized mice, exhibiting an improved tumor-killing efficacy. Mechanistically, CD70 knockout inhibits a collective lipid signaling network in CD4+ naïve and regulatory T cells involving mitochondrial integrity, cholesterol homeostasis, and fatty acid metabolism. Furthermore, ATAC-Seq delineates that CD70 is transcriptionally upregulated by NFKB2 via an Epstein-Barr virus-dependent epigenetic modification. Our findings identify CD70+ nasopharyngeal carcinoma cells as a metabolic switch that enforces the lipid-driven development, functional specialization and homeostasis of Tregs, leading to immune evasion. This study also demonstrates that CD70 blockade can act synergistically with anti-PD-1 treatment to reinvigorate T-cell immunity against nasopharyngeal carcinoma.


Persistent Identifierhttp://hdl.handle.net/10722/340837
ISSN
2023 Impact Factor: 14.7
2023 SCImago Journal Rankings: 4.887
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorGong, Lanqi-
dc.contributor.authorLuo, Jie-
dc.contributor.authorZhang, Yu-
dc.contributor.authorYang, Yuma-
dc.contributor.authorLi, Shanshan-
dc.contributor.authorFang, Xiaona-
dc.contributor.authorZhang, Baifeng-
dc.contributor.authorHuang, Jiao-
dc.contributor.authorChow, Larry Ka Yue-
dc.contributor.authorChung, Dittman-
dc.contributor.authorHuang, Jinlin-
dc.contributor.authorHuang, Cuicui-
dc.contributor.authorLiu, Qin-
dc.contributor.authorBai, Lu-
dc.contributor.authorTiu, Yuen Chak-
dc.contributor.authorWu, Pingan-
dc.contributor.authorWang, Yan-
dc.contributor.authorTsao, George Sai Wah-
dc.contributor.authorKwong, Dora Lai Wan-
dc.contributor.authorLee, Anne Wing Mui-
dc.contributor.authorDai, Wei-
dc.contributor.authorGuan, Xin Yuan-
dc.date.accessioned2024-03-11T10:47:40Z-
dc.date.available2024-03-11T10:47:40Z-
dc.date.issued2023-04-06-
dc.identifier.citationNature Communications, 2023, v. 14, n. 1-
dc.identifier.issn2041-1723-
dc.identifier.urihttp://hdl.handle.net/10722/340837-
dc.description.abstract<p>Despite the intense CD8+ T-cell infiltration in the tumor microenvironment of nasopharyngeal carcinoma, anti-PD-1 immunotherapy shows an unsatisfactory response rate in clinical trials, hindered by immunosuppressive signals. To understand how microenvironmental characteristics alter immune homeostasis and limit immunotherapy efficacy in nasopharyngeal carcinoma, here we establish a multi-center single-cell cohort based on public data, containing 357,206 cells from 50 patient samples. We reveal that nasopharyngeal carcinoma cells enhance development and suppressive activity of regulatory T cells via CD70-CD27 interaction. CD70 blocking reverts Treg-mediated suppression and thus reinvigorate CD8+ T-cell immunity. Anti-CD70+ anti-PD-1 therapy is evaluated in xenograft-derived organoids and humanized mice, exhibiting an improved tumor-killing efficacy. Mechanistically, CD70 knockout inhibits a collective lipid signaling network in CD4+ naïve and regulatory T cells involving mitochondrial integrity, cholesterol homeostasis, and fatty acid metabolism. Furthermore, ATAC-Seq delineates that CD70 is transcriptionally upregulated by NFKB2 via an Epstein-Barr virus-dependent epigenetic modification. Our findings identify CD70+ nasopharyngeal carcinoma cells as a metabolic switch that enforces the lipid-driven development, functional specialization and homeostasis of Tregs, leading to immune evasion. This study also demonstrates that CD70 blockade can act synergistically with anti-PD-1 treatment to reinvigorate T-cell immunity against nasopharyngeal carcinoma.</p>-
dc.languageeng-
dc.publisherNature Research-
dc.relation.ispartofNature Communications-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleNasopharyngeal carcinoma cells promote regulatory T cell development and suppressive activity via CD70-CD27 interaction-
dc.typeArticle-
dc.identifier.doi10.1038/s41467-023-37614-6-
dc.identifier.scopuseid_2-s2.0-85151883821-
dc.identifier.volume14-
dc.identifier.issue1-
dc.identifier.eissn2041-1723-
dc.identifier.isiWOS:001164830900052-
dc.identifier.issnl2041-1723-

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