期刊
ADVANCED BIOLOGY
卷 5, 期 9, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adbi.202100758
关键词
programmed death-1 interactome; programmed death-1 pathway; SHP-1; SHP-2; T cell activation
资金
- NIH [R21AR073494]
T cell activation is a complex process involving the PD-1 pathway, which plays a critical role in maintaining immune tolerance and dampening anti-tumor immunity. Therapeutic inhibitors targeting the PD-1 pathway have revolutionized tumor immunotherapy.
T cell activation is a fine-tuned process that involves T cell receptor and costimulation signals. To prevent undue activation of T cells, inhibitory molecules including PD-1 (programmed death 1) are induced and function as brakes for T cell signaling. In a steady state, the interaction of PD-1 with its ligands PD-L1 (B7-H1, CD274) and PD-L2 (B7-DC, CD273) maintains peripheral immune tolerance. However, the expression of PD-L1 on tumor cells and interaction with PD-1 on T cells dampen anti-tumor immunity. Therapeutic inhibitors of the PD-1 pathway have revolutionized tumor immunotherapy. Unfortunately, the majority of patients do not develop sustained anti-tumor responses. However, the knowledge about unique PD-1 interactions and their role in mediating PD-1 inhibitory signals is currently limited. Advances in the mechanistic understanding of the molecular and signaling integration of the PD-1 pathway could unleash the great potential in tumor immunotherapy by allowing the development of combinatorial approaches that target not only PD-1 and its ligands but also its unique downstream signal mediators. In this review, the current advances in understanding the mechanisms of extracellular and intracellular PD-1 interactions and their significance in potential future therapeutic approaches are discussed.
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