Tumor exosomal microRNAs thwarting anti-tumor immune responses in nasopharyngeal carcinomas
The considerable progress achieved in the past 10 years in the field of tumor biology and therapeutics has strengthened the idea that cancer is not only a cellular but also a tissue disease. This concept is likely to apply to nasopharyngeal carcinoma (NPC), characterized by the consistent expression of oncogenic viral proteins in a context of inflammation and immune escape (1). In its typical undifferentiated form, NPC is constantly associated with the Epstein-Barr virus, whose genome is contained in the nuclei of all malignant cells, but not in the surrounding tissue. Latency is the predominant mode of virus-cell interactions, meaning that most viral genes are silent in the vast majority of malignant cells. However, a small fraction of them are consistently expressed coding a handful of viral products, both viral proteins and untranslated RNAs, most of them with proven oncogenic properties. The inflammatory context of NPC is obvious for pathologists: almost all NPC primary tumors are heavily infiltrated by non-malignant leucocytes, mainly T-lymphocytes but also B lymphocytes, macrophages, dendritic cells and neutrophils. This inflammatory infiltration often disappears in metastatic lesions. The immune escape is also obvious because of the rapid proliferation of malignant cells despite the consistent expression of EBNA1, LMP1 and LMP2 which are known to be the targets of CD4+ and CD8+ cytotoxic T-cells in EBV-carriers. One interpretation of the paradox of tumor inflammation combined with tumor immune escape is that malignant cells in the primary tumor benefit to some extent from the proximity of leucocytes while developing mechanisms of immune escape.