The First Shall (Be) Last: Understanding Durable T Cell Responses in Immunotherapy.

Efforts to understand how cancer immunotherapy restores anti-tumor T cell responses have largely concentrated on assessing the reactivation of dysfunctional T cells. In this issue of Immunity, Kurtulus et al. (2019) and Siddiqui et al. (2019) provide evidence that durable anti-tumor responses require less differentiated T cells that express the transcription factor Tcf1 and sustain the tumor-reactive T cell pool.