Target intelligence / Profile preview

Programmed cell death protein 1 (PD-1) receptor (PD-1)

Target
PD-1
Molecular classification
Immune checkpoint receptor, Immunoglobulin superfamily, CD antigen, Receptor
01

Overview

Programmed cell death protein 1 (PD-1) is a cell surface receptor belonging to the immunoglobulin superfamily that acts as a critical immune checkpoint [3, 12]. Primarily expressed on activated T cells, B cells, and myeloid cells, its fundamental biological role is to down-regulate the immune response and promote self-tolerance by suppressing T-cell inflammatory activity [3, 11]. This inhibitory signaling is triggered when PD-1 binds to its ligands, PD-L1 or PD-L2, which are often overexpressed by tumor cells to evade immune detection and induce T-cell exhaustion [9, 13, 15]. Therapeutic anti-PD-1 antibodies, such as pembrolizumab and nivolumab, block this interaction, effectively removing the brake on the immune system and restoring the ability of cytotoxic T cells to recognize and eliminate cancer cells [10, 14]. While these therapies have significantly improved outcomes in various malignancies, they are associated with a unique spectrum of immune-related adverse events (irAEs) resulting from the non-specific activation of the immune system against healthy tissues [1, 4, 7].

Other names
PDCD1CD279Programmed cell death 1SLEB2hPD-1hPD-lhSLE1
02

Mechanism of action

PD-1 inhibition/blockade: Monoclonal antibodies bind to the PD-1 receptor on T cells, preventing its interaction with ligands PD-L1 and PD-L2, thereby restoring T-cell mediated anti-tumor immune responses [3, 10, 13].

03

Biological functions

Immune responseT-cell regulationApoptosisSelf-tolerance
04

Disease associations

CancerAutoimmune diseaseInfection
05

Safety considerations

Immune-related adverse events (irAEs)PneumonitisColitisHepatitisEndocrinopathyDermatitisMyocarditisNeurotoxicity
06

Interacting drugs

11 more in the full profile.

07

Biomarkers

PD-L1 expression (TPS/CPS)Microsatellite instability-high (MSI-H)Mismatch repair deficiency (dMMR)Tumor mutational burden (TMB)Absolute lymphocyte count (ALC)Absolute eosinophil count (AEC)

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