We previously showed that in patients, nitric oxide synthase activity (NOS2) promoted nasopharyngeal tumor growth (NPC). Tumor necrosis factor (TNFα) is a pro-inflammatory cytokine which engages nitric oxide (NO∗) in several carcinogenic processes. In NPC patients, TNFα synthesis associates with poor survival. Here, we aimed at determining whether TNFα signaling inhibition could alter NOS2 dependent NPC growth in vitro. For this purpose, TNFα influence on nitrite production and tumor cell proliferation were analyzed. We observed that monocytes/macrophages (Mo/Ma) and primary tumor biopsies, isolated from patients, synthesized significant amounts of nitrites. Endogenous TNFα neutralization with an anti-TNFα monoclonal antibody (mAb) successfully inhibited nitrites synthesis by Mo/Ma and tumor explants. Recombinant TNFα (rTNFα) enhanced nitrites synthesis and C666-1 NPC cells proliferation. Treatment with the NOS2 selective inhibitor (1400 W) and an anti-TNFα mAb potently inhibited rTNFα induced C666-1 proliferation and nitrites synthesis. Strikingly, patients tumors explants treated with the anti-TNFα mAb displayed reduced proliferation as indicated by Ki67 index. Altogether, our results define Mo/Ma and the primary tumor as major sources of circulating NO∗ in NPC patients and support the idea that antibody dependent inhibition of the TNFα/NOS2 inflammatory pathway may alter nasopharyngeal carcinoma tumor growth.
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