What is the difference between Programmed Death-Ligand 1 (PDL-1) and Programmed Death-1 (PD-1)?

Difference Between PD-L1 and PD-1

PD-1 is a receptor expressed on immune cells (particularly T cells) that functions as an inhibitory checkpoint, while PD-L1 is a ligand expressed on tumor cells and antigen-presenting cells that binds to PD-1 to suppress immune responses. 1

Molecular Identity and Location

PD-1 (Programmed Death-1)

• PD-1 is a cell surface receptor that functions as a T cell checkpoint and negatively regulates T cell function 1
• Expressed on activated immune cells including T cells, B cells, dendritic cells, and natural killer cells 2
• Acts as an inhibitory signaling protein that prevents exacerbated immune activation and autoimmunity 3

PD-L1 (Programmed Death-Ligand 1)

• PD-L1 is a co-regulatory molecule and ligand that binds to the PD-1 receptor 4
• Expressed on tumor cells and antigen-presenting cells in the tumor microenvironment 1
• Often overexpressed on various cancer cells, playing a key role in modulating immune responses 4

Functional Relationship

The PD-1/PD-L1 Axis

• When PD-L1 binds to PD-1, it activates downstream signaling pathways that inhibit T cell activation and suppress immune responses 5
• This interaction inhibits T-cell–mediated cell death, allowing tumor cells to evade immune surveillance 4
• Blockade of the PD-1/PD-L1 axis promotes T cell activation and immune killing of cancer cells 1

Clinical Implications for Immunotherapy

Therapeutic Targeting

• Checkpoint inhibitor antibodies can target either PD-1 or PD-L1 to block their interaction 4
• Anti-PD-1 antibodies include nivolumab and pembrolizumab 1
• Anti-PD-L1 antibodies include avelumab and atezolizumab 1
• Both approaches restore T cell-mediated cytotoxicity by preventing the inhibitory signal 6

Biomarker Testing

• PD-L1 expression testing is recommended for all patients with newly diagnosed advanced NSCLC to guide treatment decisions 4
• PD-L1 expression is measured using immunohistochemistry (IHC) assays evaluating membranous immunostaining of tumor cells 4
• PD-L1 is not a perfect biomarker—less than half of biomarker-selected patients benefit from treatment, and some responses occur in biomarker-negative cohorts 4

Important Clinical Caveat

• PD-L1 expression did not consistently correlate with response to PD-1 inhibitors in clinical trials such as Checkmate 025 1
• The relationship between PD-1/PD-L1 expression, microsatellite instability, and tumor mutational burden is complex and differs according to tumor types 1