PD-1 signaling pathway in sepsis: Does it have a future?

Abstract

Sepsis is characterized by high mortality and poor prognosis and is one of the leading causes of death among patients in the intensive care unit (ICU). In the past, drugs that block early inflammatory responses have done little to reverse the progression of sepsis. Programmed cell death receptor 1 (PD-1) and its two ligands, programmed cell death receptor ligand 1(PD-L1) and programmed cell death receptor ligand 2 (PD-L2), are negative regulatory factors of the immune response of the body. Recently, the role of the PD-1 signaling pathway in sepsis has been widely studied. Studies showed that the PD-1 signaling pathways are closely related to the mortality and prognosis of sepsis patients. In the immunotherapy of sepsis, whether in animal experiments or clinical trials, anti-PD-1/PD-L1 antibodies have shown good promise. In this review, firstly, we focus on the immunosuppressive mechanism of sepsis and the structure and function of the PD-1 signaling pathway. The variety of the PD-1 signaling pathways in sepsis is introduced. Then, the relationship between the PD-1 signaling pathway and immune cells and organ dysfunction and the regulatory factors of the PD-1 signaling pathway in sepsis is discussed. Finally, the application of the PD-1 signaling pathway in sepsis is specifically emphasized.

Keywords: Immunosuppression; Immunotherapy; Programmed cell death receptor 1; Programmed cell death receptor ligand 1; Sepsis.