Fig. 7. TRIM21 overexpression indicates poor survival and is associated with tumour relapse.

a TRIM21 and VDAC2 protein expression was evaluated by IHC staining in 46 NPC tumour tissues (scale bar, 50 μm). b VDAC2 IHC scores in NPC tissues with high and low TRIM21 expression. The data are presented as the mean ± SD; two-tailed Mann–Whitney test). c, d Representative images (scale bar, 100 μm) and quantitative results of multiplex immunohistochemistry for CD3⁺, CD8⁺, CD3⁺CD8⁺ and CD11c⁺ cells in 46 NPC tissues with high and low TRIM21 expression (the data are presented as the mean ± SEM; two-tailed unpaired t test). e Association between TRIM21 expression and locoregional recurrence status after radical chemoradiotherapy in a cohort of 355 NPC samples (two-sided χ² test). f–h Kaplan–Meier analysis of locoregional recurrence-free (f), disease-free (g) and overall (h) survival based on the TRIM21 expression level (log-rank test). i Proposed working model of TRIM21. Bulk and scRNA-seq revealed that TRIM21 acts as a negative regulator of IFN signalling and the radiation response in NPC cells. Mechanistically, TRIM21 facilitates the ubiquitination and degradation of VDAC2 and inhibits pore formation by VDAC2 oligomers for mtDNA release, thus suppressing radiation-induced STING–type-I IFN signalling and antitumour immune responses. High TRIM21 expression is associated with impaired antitumour immunity and poor survival in NPC patients.