Abstract

Nasopharyngeal carcinoma (NPC) arises from a unique anatomical site with heavy infiltration of leucocytes, predominantly T-lymphocytes, together with other stromal cells. Undifferentiated NPC is the prevalent histological subtype (>98%) in endemic areas in Southern China including Hong Kong. Epstein–Barr virus (EBV) infection is closely associated with undifferentiated NPC. EBV infection in NPC is generally latent in nature. Expression of viral gene products may facilitate the malignant transformation of premalignant nasopharyngeal epithelium to NPC cells. Among the latent EBV gene products, the high expression of EBV-encoded BART-microRNAs in NPC is strongly implicated in NPC pathogenesis. A unique tumor microenvironment (TME) infiltrated heavily with T-lymphocytes and other stromal cells is believed to be involved to support growth of NPC in patients and latent EBV infection in NPC. Various cytokines secreted by EBV-infected NPC cells and the infiltrated stromal cells in the TME are involved in the recruitment of the rich cellular components to the tumor stroma. The dynamic and reciprocal interaction of cancer cells with stromal cells in the TME has been postulated to support EBV infection and modulate growth and invasive properties of NPC cells. Delineating the complex cancer cell–stromal cell interaction in NPC may reveal novel therapeutic targets effective for NPC treatment.

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