TRIM21 inhibits irradiation-induced mitochondrial DNA release and impairs antitumour immunity in nasopharyngeal carcinoma tumour models

Jun-Yan Li, Yin Zhao, Sha Gong, Miao-Miao Wang, Xu Liu, Qing-Mei He, Ying-Qin Li, Sheng-Yan Huang, Han Qiao, Xi-Rong Tan, Ming-Liang Ye, Xun-Hua Zhu, Shi-Wei He, Qian Li, Ye-Lin Liang, Kai-Lin Chen, Sai-Wei Huang, Qing-Jie Li, Jun Ma () and Na Liu ()
Additional contact information
Jun-Yan Li: Sun Yat-sen University Cancer Center
Yin Zhao: Sun Yat-sen University Cancer Center
Sha Gong: Sun Yat-sen University Cancer Center
Miao-Miao Wang: Sun Yat-sen University Cancer Center
Xu Liu: Sun Yat-sen University Cancer Center
Qing-Mei He: Sun Yat-sen University Cancer Center
Ying-Qin Li: Sun Yat-sen University Cancer Center
Sheng-Yan Huang: Sun Yat-sen University Cancer Center
Han Qiao: Sun Yat-sen University Cancer Center
Xi-Rong Tan: Sun Yat-sen University Cancer Center
Ming-Liang Ye: Sun Yat-sen University Cancer Center
Xun-Hua Zhu: Sun Yat-sen University Cancer Center
Shi-Wei He: Sun Yat-sen University Cancer Center
Qian Li: Sun Yat-sen University Cancer Center
Ye-Lin Liang: Sun Yat-sen University Cancer Center
Kai-Lin Chen: Sun Yat-sen University Cancer Center
Sai-Wei Huang: Sun Yat-sen University Cancer Center
Qing-Jie Li: Sun Yat-sen University Cancer Center
Jun Ma: Sun Yat-sen University Cancer Center
Na Liu: Sun Yat-sen University Cancer Center

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Although radiotherapy can promote antitumour immunity, the mechanisms underlying this phenomenon remain unclear. Here, we demonstrate that the expression of the E3 ubiquitin ligase, tumour cell-intrinsic tripartite motif-containing 21 (TRIM21) in tumours, is inversely associated with the response to radiation and CD8+ T cell-mediated antitumour immunity in nasopharyngeal carcinoma (NPC). Knockout of TRIM21 modulates the cGAS/STING cytosolic DNA sensing pathway, potentiates the antigen-presenting capacity of NPC cells, and activates cytotoxic T cell-mediated antitumour immunity in response to radiation. Mechanistically, TRIM21 promotes the degradation of the mitochondrial voltage-dependent anion-selective channel protein 2 (VDAC2) via K48-linked ubiquitination, which inhibits pore formation by VDAC2 oligomers for mitochondrial DNA (mtDNA) release, thereby inhibiting type-I interferon responses following radiation exposure. In patients with NPC, high TRIM21 expression was associated with poor prognosis and early tumour relapse after radiotherapy. Our findings reveal a critical role of TRIM21 in radiation-induced antitumour immunity, providing potential targets for improving the efficacy of radiotherapy in patients with NPC.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-36523-y 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_s41467-023-36523-y

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

DOI: 10.1038/s41467-023-36523-y

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 ().