Nasopharyngeal carcinoma (NPC) is the most common EBV (Epstein-Barr virus) related epithelial malignant tumor. Over 90% of patients diagnosed with undifferentiated nasopharyngeal carcinoma are infected with EB virus. EBV infection of nasopharyngeal carcinoma leads to the remodeling of the immune microenvironment. There are now numerous research mechanisms regarding the remodeling of the immune microenvironment by EBV. This article systematically integrates single-cell transcriptomics, spatial metabolomics, and clinical research evidence, and from four dimensions: effector cell exhaustion, inhibitory cell expansion, metabolic reprogramming, and spatial organization of tertiary lymphoid structures, it analyzes the multi-level mechanisms by which EBV remodels the immune microenvironment. The core findings indicate that EBV constructs a multi-target and multi-level coordinated regulatory network through its encoded proteins (LMP1, LMP2A, EBNA1, and BRRF2) and non-coding RNAs (miR-BARTs and circRNAs). This regulatory mechanism dynamically evolves at different stages of the disease, with synergistic effects during the latent and lytic phases, forming an immunosuppressive microenvironment. However, the limitations in mechanism understanding have led to difficulties in clinical translation and drug use. The objective response rate of PD-1 inhibitors is only 20–30%. Single-target blockade is difficult to improve treatment efficacy. Therefore, based on previous research data, we propose that in the future, we need to shift from single-target blockade to the overall ecosystem regulation of the immune microenvironment, combined with targeted inhibition of immune checkpoints, chemokine axes, metabolic nodes, and viral own products, and based on EBV DNA load and TLS status for precise stratification. This is expected to break through the current treatment limitations and promote EBV-positive nasopharyngeal carcinoma from empirical treatment to mechanism-driven precise immunotherapy intervention.
Yudie et al. (Thu,) studied this question.