Chronic antigen stimulation during persistent infections or cancer leads to functional exhaustion of CD8 T cells. The inhibitory receptor PD-1 plays a major role in this T cell dysfunction and blockade of this inhibitory pathway restores function in exhausted T cells. T cell exhaustion and the role of PD-1 in chronic infection were first documented in the mouse model of chronic LCMV infection and these findings were then extended to chronic viral infections in non-human primates and humans. In this talk I will discuss combinatorial strategies that enhance PD-1 directed immunotherapy and describe how PD-1 blockade acts not only at the level of increasing T cell numbers but plays a key role in target cell elimination. An interesting aspect of PD-1 biology is that PD-1 is also expressed during the early phase of T cell activation. In this talk I will also discuss how this early PD-1 expression is regulated and its potential role in CD8 T cell differentiation.

Citation Format: Rafi Ahmed. T cell memory and exhaustion. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr IA23.