Can T cells be too exhausted to fight back?

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Science  02 Dec 2016:
Vol. 354, Issue 6316, pp. 1104-1105
DOI: 10.1126/science.aal3204

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When T cells are persistently activated by antigen, such as during chronic infection or in cancer, they can become functionally incapable of performing their effector activities, a condition called T cell exhaustion. Exhaustion therefore thwarts optimal immune control of infection and tumors. There is a need to learn more about the molecular factors that drive T cell exhaustion and just how malleable T cell immunity is once exhaustion is established. On pages 1165 and 1160 of this issue, Sen et al. (1) and Pauken et al. (2), respectively, demonstrate that T cell exhaustion represents a stable differentiation state, underpinned by the apparently irreversible installation of an exhaustion-specific genetic landscape. This implies that perhaps in a majority of cases of persistent immune activation, T cells are too exhausted to fight back against cancer or pathogens.