ICAM1 promotes the invasion and metastasis of Epstein-Barr virus (EBV) positive nasopharyngeal carcinoma (NPC) cells by regulating the CCR7-JAK3/STAT3 axis to modulate PD-L1 expression.

Abstract

Background: In patients with locally advanced, metastatic, or recurrent nasopharyngeal carcinoma (NPC), immunotherapy, especially with programmed cell death ligand 1 (PD-L1) inhibitors, is increasingly being applied for clinical treatment and has shown promising results. Intercellular adhesion molecule 1 (ICAM1) is closely associated with the occurrence and progression of NPC induced by Epstein-Barr virus (EBV) infection and is related to the high expression of PD-L1 and immune suppression in tumour tissues. However, the specific mechanisms are unclear.

Methodology: We used two GEO datasets, GSE68799 and GSE102349, for bioinformatics analysis and performed immunohistochemistry (IHC) on 75 clinical NPC tissue samples. The results from both methods were combined to validate the relationships among ICAM, PD-L1, and patients with late-stage EBV-positive NPC. To elucidate the underlying mechanism, we used Western blotting, coimmunoprecipitation (Co-IP), and immunofluorescence (IF) to investigate the role of ICAM1 in the promotion of NPC cell malignancy.

Results: We found that ICAM1 was highly expressed in EBV-positive NPC tissues and was associated with poor prognosis. Silencing ICAM1 expression decreased the malignant behaviour of NPC cells and PD-L1 expression. The mechanistic study revealed that ICAM1 increased PD-L1 expression, especially at the cell membrane, by activating the JAK3/STAT3 signalling pathway through interactions with CCR7 and its ligands CCL19 and CCL21.

Conclusion: The results of this study indicate that ICAM1 may serve as a therapeutic target for patients with recurrent, metastatic EBV-positive NPC.