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

Lanqi Gong, Jie Luo, Yu Zhang, Yuma Yang, Shanshan Li, Xiaona Fang, Baifeng Zhang, Jiao Huang, Larry Ka-Yue Chow, Dittman Chung, Jinlin Huang, Cuicui Huang, Qin Liu, Lu Bai, Yuen Chak Tiu, Pingan Wu, Yan Wang, George Sai-Wah Tsao, Dora Lai-wan Kwong, Anne Wing-Mui Lee, Wei Dai and Xin-Yuan Guan ()
Additional contact information
Lanqi Gong: The University of Hong Kong
Jie Luo: The University of Hong Kong
Yu Zhang: Sun Yat-sen University Cancer Center
Yuma Yang: The University of Hong Kong
Shanshan Li: The University of Hong Kong-Shenzhen Hospital
Xiaona Fang: The University of Hong Kong
Baifeng Zhang: The University of Hong Kong
Jiao Huang: The University of Hong Kong
Larry Ka-Yue Chow: The University of Hong Kong
Dittman Chung: The University of Hong Kong
Jinlin Huang: The University of Hong Kong
Cuicui Huang: The University of Hong Kong
Qin Liu: The University of Hong Kong
Lu Bai: The University of Hong Kong
Yuen Chak Tiu: The University of Hong Kong
Pingan Wu: The University of Hong Kong-Shenzhen Hospital
Yan Wang: The University of Hong Kong-Shenzhen Hospital
George Sai-Wah Tsao: The University of Hong Kong
Dora Lai-wan Kwong: The University of Hong Kong
Anne Wing-Mui Lee: The University of Hong Kong
Wei Dai: The University of Hong Kong
Xin-Yuan Guan: The University of Hong Kong

Nature Communications, 2023, vol. 14, issue 1, 1-24

Abstract: 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-37614-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37614-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-37614-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().