Kuchroo et al. focused on gaining a deeper understanding of PD-1’s role in restraining Treg function during checkpoint blockade treatment that can lead to immune-related adverse events (irAEs) during cancer treatment. The review covered the mechanism of PD-1 signaling in Tregs, focusing on its impact on the PI3K-Akt pathway and the role of PD-1 in promoting tolerance to self and regulation of T cell exhaustion. Several potential strategies to modulate PD-1 signaling to enhance or maintain antitumor immunity while limiting irAEs that can result in treatment discontinuation were proposed.
Contributed by Katherine Turner
ABSTRACT: Immune checkpoint blockade has demonstrated success in treating cancer but can lead to immune-related adverse events (irAEs), illustrating the centrality of these pathways in tolerance. Here, we describe programmed cell death protein 1 (PD-1) control of T cell responses, focusing on its unique restraint of regulatory T cell function. We examine successes and limitations of checkpoint blockade immunotherapy and review clinical and mechanistic features of irAEs. Last, we discuss strategies to modulate PD-1 blockade to enhance antitumor immunity while limiting autoimmunity.