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.
Author Info: (1) Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. Evergrande Center for Immunological Diseases, Harvard Medical School and Brigham and Wom
Author Info: (1) Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. Evergrande Center for Immunological Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA. (2) Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT, USA. Broad Institute of MIT and Harvard University, Cambridge, MA, USA. (3) Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. Evergrande Center for Immunological Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA. Broad Institute of MIT and Harvard University, Cambridge, MA, USA. Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. (4) Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT, USA.
