TNF-α is critical for antitumor but not antiviral T cell immunity in mice

Thomas Calzascia, Marc Pellegrini, Håkan Hall, Laurent Sabbagh, Nobuyuki Ono, Alisha R. Elford, Tak W. Mak, Pamela S. Ohashi

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TNF-α antagonists are widely used in the treatment of inflammatory and autoimmune diseases, but their use is associated with reactivation of latent infections. This highlights the importance of TNF-α in immunity to certain pathogens and raises concerns that critical aspects of immune function are impaired in its absence. Unfortunately, the role of TNF-α in the regulation of T cell responses is clouded by a myriad of contradictory reports. Here, we show a role for TNF-α and its receptors, TNFR1 and TNFR2, specifically in antitumor immunity. TNF-α-deficient mice exhibited normal antiviral responses associated with strong inflammation. However, TNF-α/TNFR1-mediated signals on APCs and TNF-α/TNFR2 signals on T cells were critically required for effective priming, proliferation, and recruitment of tumor-specific T cells. Furthermore, in the absence of TNF-α signaling, tumor immune surveillance was severely abrogated. Finally, treatment with a CD40 agonist alone or in combination with TLR2 stimuli was able to rescue proliferation of TNF-α-deficient T cells. Therefore, TNF-α signaling may be required only for immune responses in conditions of limited immunostimulatory capacity, such as tumor surveillance. Importantly, these results suggest that prolonged continuous TNF-α blockade in patients may have long-term complications, including potential tumor development or progression.

元の言語英語
ページ(範囲)3833-3845
ページ数13
ジャーナルJournal of Clinical Investigation
117
発行部数12
DOI
出版物ステータス出版済み - 12 1 2007

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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    Calzascia, T., Pellegrini, M., Hall, H., Sabbagh, L., Ono, N., Elford, A. R., Mak, T. W., & Ohashi, P. S. (2007). TNF-α is critical for antitumor but not antiviral T cell immunity in mice. Journal of Clinical Investigation, 117(12), 3833-3845. https://doi.org/10.1172/JCI32567