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

T Calzascia, M Pellegrini, H Hall… - The Journal of …, 2007 - Am Soc Clin Investig
T Calzascia, M Pellegrini, H Hall, L Sabbagh, N Ono, AR Elford, TW Mak, PS Ohashi
The Journal of clinical investigation, 2007Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation