Like other human solid tumors, nasopharyngeal carcinoma (NPC) is a tissue and a systemic disease as much as a cell disease. Tumor cell population in NPC is highly heterogeneous. Heavy infiltration by non-malignant leucocytes results at least in part from the production of abundant inflammatory cytokines by the malignant epithelial cells. There is indirect evidence that interactions between stromal and malignant cells contribute to tumor development. Peripheral blood samples collected from NPC patients contain multiple products derived from the tumor, including cytokines, non-cytokine tumor proteins, tumor exosomes and viral nucleic acids. These products represent a potential source of biomarkers for assessment of tumor aggressiveness, indirect exploration of cellular interactions and monitoring of tumor response to therapeutic agents. Most NPC patients are immunocompetent with evidence of active humoral and cellular immune responses against EBV-antigens at the systemic level. Tumor development is facilitated by local immunosuppressive factors which are not fully understood. Local accumulation of regulatory T-cells is probably one important factor. At least two NPC tumor products are suspected to contribute to their expansion, the cytokine CCL20 and the tumor exosomes carrying galectin 9. In the future, new therapeutic modalities will probably aim at breaking immune tolerance or at blocking cellular interactions critical for tumor growth.
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