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Tumor Biology |
Graduate Institute of Microbiology [Y-T. H., J. L., Y. C., J-Y. C., C-H. T.] and Departments of Otolaryngology [T-S. S.] and Pathology [C-L. C.], College of Medicine, National Taiwan University, Taipei, Taiwan
Nasopharyngeal carcinoma (NPC) is an epithelial cancer that is causally associated with Epstein-Barr virus (EBV) infection. NPC tumor biopsies are characterized histopathologically by an abundant infiltration of nonmalignant lymphocytes. We analyzed the expression of various cytokines in NPC tissues to investigate the interaction of the infiltrating lymphocytes and tumor cells. Analysis using reverse transcriptase-PCR revealed the expression of a panel of cytokines in the NPC biopsies: interleukin (IL)-1
, IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IFN-
, tumor necrosis factor-, transforming growth factor-ß, and IL-1 receptor types I and II. Elevated expression of IL-1 and IL-1ß was observed in primary tumors and NPC metastases compared to control tissues. Interestingly, this increased expression correlated with the EBV-encoded viral IL-10 transcript. To determine which cells were responsible for producing IL-1, we determined the cellular constituents of NPC biopsies by immunoflow cytometric analysis. On the basis of data from these analyses, the three major specific cell populations, epithelial cells, CD4+ T cells, and CD8+ T cells, were selected from five NPC tumors using specific, antibody-coated paramagnetic beads. Reverse transcriptase-PCR of RNA from these fractionated cells showed that transcripts of IL-1 and IL-1ß were present not only in the malignant epithelial cells but also in CD4+ T cells infiltrating the tumor, a finding confirmed by immunohistochemical staining. We hypothesize that the unusual synthesis of IL-1 and IL-1ß by EBV-positive epithelial cells as well as by CD4+ T cells might contribute to lymphocyte infiltration and/or tumor growth during NPC development.
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