AI Summary
The transcription factor NFAT5 regulates T cell exhaustion in cancer but not in chronic viral infection. CD8+ T cell exhaustion is a dysfunctional state caused by chronic exposure to antigen and signals from the microenvironment. Exhaustion can occur in both cancer and chronic infection and is correlated with negative outcomes in cancer patients. The differences in exhaustion-promoting signals between tumors and infection are not well understood. NFAT5 is upregulated in CD8+ T cells in human and mouse tumors.
The transcription factor NFAT5 regulates T cell exhaustion, a dysfunctional state caused by chronic exposure to antigen and other signals, during cancer but not during chronic viral infection.
CD8+ T cell exhaustion is a dysfunctional differentiation state that is caused by chronic exposure to antigen and signals from the microenvironment1. CD8+ T cell exhaustion, driven by chronic antigen exposure, can occur in both cancer and chronic infection and is correlated with negative outcomes in patients with cancer1,2. Chronic infection is frequently used as a model to study T cell exhaustion, and despite differences in microenvironmental conditions, lessons learned from infection are often applied to cancer settings. Yet how exhaustion-promoting signals differ between tumors and infection is not well understood. In this issue of Nature Immunology, Tillé et al.3 show that the transcription factor NFAT5, which is upregulated in CD8+ T cells in human and mouse tumors