Wartewig, T. and Ruland, J. (2019). Trends Immunol 40, 403-414.
The inhibitory receptor PD-1 is critical to balancing antigen-induced T cell activation; its inhibition is currently being explored to enhance antitumor T cell immunity with certain successful outcomes. However, PD-1 has also emerged as a central tumor suppressor in T cell lymphomas, where the tumor cell originates from a T cell itself. These aggressive cancers are frequently characterized by oncogenic mutations in T cell receptor (TCR) signaling pathways. PD-1 activity within malignant T cells can negatively regulate the PI3K/AKT and PKCθ/NF-κB tumor survival pathways and PD-1 is frequently inactivated in this human malignancy. This review summarizes current insights into oncogenic T cell signaling, discusses tumor-suppressive functions and mechanisms of PD-1 in T cell lymphomagenesis, and addresses potential unwanted effects caused by PD-1 checkpoint inhibition.