Accelerated tumor growth and lymphatic spread of B16 melanomas in TNF-transgenic mice 4015

Description As many as one in five human cancers have been linked to chronic inflammatory processes. Tumor necrosis factor (TNF)-transgenic (TNFtg) mice are a well-established model of chronic systemic inflammation, with involvement of joints and other organ systems. Although TNF can display both pro- and anti-tumoral effects, TNF signaling was recently linked to epithelial cell tumorigenesis and progression. To assess the effect of TNF overexpression on melanoma growth in vivo, we investigated the growth of transplantable B16 melanomas in TNFtg mice (3647 single-copy strain). B16 (F1 and F10 subline) cells were injected into the hind paws of TNFtg mice and non-transgenic (NT) littermates at 8-12 weeks of age (early arthritis). TNFtg mice displayed highly accelerated B16 primary tumor growth compared to NT littermates (max dimension 10.3±2.7mm vs 3.7±1.5mm at week 2, p < 0.0001), and accelerated tumor-draining lymph node (TDLN) invasion (8/19 vs 2/21 positive TDLNs in TNFtg vs NT mice, p < 0.05). To test whether the observed effects were linked to TNF overexpression per se or to the inflamed microenvironment in the arthritic paws, we also compared growth of tumors injected in the lower flank, and observed no primary tumor growth differences (251±155mm3 vs 319±178mm3 tumor volume in TNFtg vs NT, p = 0.3). Overall, these results highlight a significant effect of TNF, and specifically of the TNF-driven inflammatory microenvironment, in B16 melanoma growth. Funding Sources Supported by CMSRU and Camden Cancer Research Center pilot funds Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)