PD‐1: A critical player and target for immune normalization

Abstract

Immune system imbalances contribute to the pathogenesis of several different diseases, and immunotherapy shows great therapeutic efficacy against tumours and infectious diseases with immune‐mediated derivations. In recent years, molecules targeting the programmed cell death protein 1 (PD‐1) immune checkpoint have attracted much attention, and related signalling pathways have been studied clearly. At present, several inhibitors and antibodies targeting PD‐1 have been utilized as anti‐tumour therapies. However, increasing evidence indicates that PD‐1 blockade also has different degrees of adverse side effects, and these new explorations into the therapeutic safety of PD‐1 inhibitors contribute to the emerging concept that immune normalization, rather than immune enhancement, is the ultimate goal of disease treatment. In this review, we summarize recent advancements in PD‐1 research with regard to immune normalization and targeted therapy.

Probing the Immunoreceptor Tyrosine-Based Inhibition Motif Interaction Protein Partners with Proteomics

“…Upon binding to PD-L1, PD-1 recruits the tyrosine phosphatase SHP2 through ITSM, subsequently dephosphorylating numerous key components of the TCR signaling pathway [14,15]. This process inhibits the proliferation and activity of CD4 and CD8 T cells, thereby negatively regulating the immune response [16,17]. The protein phosphatase of SHP2 is essential to the Ras-ERK1/2 signaling pathway [18][19][20][21].…”