Ablation of TNF or lymphotoxin signaling and the frequency of spontaneous tumors in p53-deficient mice

TNF plays diverse and contrasting roles in cancer, promoting skin carcinogenesis and metastasis, but also possessing potent antitumor effects in mice. TNF via TNFR1 axis induces NF kappa B, and may contribute to inflammation-facilitated neoplasia. On the other hand, lymphomas are cited as rare complications of anti-TNF therapy in humans. In order to address possible modulating role of TNF and of a related cytokine, LT alpha, in spontaneous tumorigenesis, we compared mice with p53-TNF, p53-LT alpha, p53-TNFR1 and p53-TNF-LT combined deficiencies. Unexpectedly, neither of these mice showed significant modulation of their survival or shift in the spectrum of emerging tumors, as compared to p53-deficient mice, arguing against direct link between TNF blockade and lymphoma development. (C) 2008 Elsevier Ireland Ltd. All rights reserved.