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PD-1 PD-L1 pathway diagram image immune checkpoint

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Here are two clear diagrams of the PD-1/PD-L1 pathway:

PD-1 / PD-L1 Immune Checkpoint Pathway

Diagram 1 - Clinical Mechanism (NCI)

Left panel: PD-L1 on the tumor cell surface binds PD-1 on the T cell. This interaction sends an inhibitory signal that shuts down the T cell - the tumor escapes immune killing.

Right panel: Anti-PD-L1 or Anti-PD-1 antibodies block the binding. The T cell remains active and kills the tumor cell.

Diagram 2 - Intracellular Signaling Cascade

When PD-L1 (tumor cell) binds PD-1 (T cell), the cytoplasmic tail of PD-1 contains two key motifs:

ITIM (immunoreceptor tyrosine-based inhibitory motif)
ITSM (immunoreceptor tyrosine-based switch motif)

These get phosphorylated and recruit SHP-2 (a phosphatase), which then:

Inhibits PI3K → AKT signaling (reduces cell survival)
Inhibits Ras → MAPK → ERK signaling (reduces proliferation)
Inhibits PTEN indirectly

Net result: T cell exhaustion, reduced cytokine production, and impaired cytotoxic function - the tumor survives.

Key Takeaways

Component	Location	Role
PD-1	T cell surface	Inhibitory receptor
PD-L1 (B7-H1)	Tumor cells, APCs	Ligand that silences T cells
PD-L2 (B7-DC)	Dendritic cells	Second ligand for PD-1
Anti-PD-1 drugs	-	Nivolumab, Pembrolizumab
Anti-PD-L1 drugs	-	Atezolizumab, Durvalumab, Avelumab

The PD-1/PD-L1 axis is upregulated by IFN-γ in the tumor microenvironment, which is the tumor's adaptive mechanism to resist immune attack. Checkpoint inhibitors targeting this pathway are now standard of care in many cancers (NSCLC, melanoma, urothelial cancer, and others) as covered in PMC review literature.

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