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High-risk EBV promotes immune evasion in nasopharyngeal carcinoma by upregulating HLA-DP via the encoded BALF2-HR variant

ABSTRACT: Nasopharyngeal carcinoma (NPC) is prevalent in East and Southeast Asia, with genetic factors playing a significant role in its occurrence. The HLA gene region on chromosome 6 is linked to NPC susceptibility, but the mechanisms remain unclear. Epstein-Barr virus (EBV) infection is a well-established cause, with 95% of NPC patients being EBV-positive. Three key variations in the EBV genome (162215_C, 162476_C, 163364_T) in the BALF2 gene are strongly associated with NPC risk. This study finds that the high-risk BALF2 variant (BALF2-HR) upregulates HLA class II molecules, such as HLA-DP, which interacts with LAG-3 on CD8⁺ T cells, inhibiting cytokine secretion and promoting T cell exhaustion, leading to immune evasion and reduced anti-PD-1 efficacy. BALF2-HR also enhances HLA-DP transcription by binding to KPNA2 and facilitating CIITA nuclear translocation. Conjunctive immunotherapy with anti-LAG-3 and anti-PD-1 antibodies significantly improves NPC treatment. This work introduces a new therapeutic strategy for NPC and insights into infection-associated cancers.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Nasopharyngeal Epithelial Cell

SUBMITTER: Wei Xiong

LAB HEAD: Wei Xiong

PROVIDER: PXD074503 | Pride | 2026-02-17

REPOSITORIES: Pride

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			Action	DRS
	XA02500GI_BALF_1.raw	Raw
	XA02500GI_BALF_2.raw	Raw
	checksum.txt	Txt
	search.tsv.txt	Txt

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