PD-L1 Signaling in Cancer Cell Immune Evasion

Programmed death-ligand 1 (PD-L1) is a transmembrane protein expressed by many tumour cells that binds to the PD-1 receptor on T lymphocytes, thereby dampening antitumour immune responses. Beyond this canonical immune-checkpoint function, PD-L1 engages a network of intracellular signalling pathways that modulate cancer cell survival, proliferation, metastatic potential and resistance to therapy. These tumour-intrinsic signals intersect with processes such as epithelial–mesenchymal transition (EMT), autophagy and cancer stemness, creating feedback loops that both enhance immune evasion and foster more aggressive phenotypes. Regulation of PD-L1 surface density via growth factor-dependent trafficking further refines its inhibitory capacity. Clinically, blockade of PD-1/PD-L1 has transformed treatment paradigms across multiple malignancies, yet variable response rates and emerging mechanistic insights highlight the need for combination approaches targeting both immune and tumour-intrinsic functions of PD-L1.

Research from Nature Portfolio

No recent Nature Portfolio content available.

PD-L1 Signaling in Cancer Cell Immune Evasion publication trend

The graph below shows the total number of articles in pd-l1 signaling in cancer cell immune evasion across all publications each year (not limited to Nature Index journals).

Technical terms

PD-L1: A ligand on tumour cells that binds to the PD-1 receptor on T cells, inhibiting their activity.

Immune checkpoint: A regulatory pathway by which immune responses are modulated to prevent overactivation and autoimmunity.

Epithelial–mesenchymal transition (EMT): A process whereby epithelial cells acquire mesenchymal characteristics, enhancing motility and invasiveness.

Autophagy: A cellular degradation pathway that recycles organelles and proteins, often co-opted by cancer cells for survival under stress.

Extracellular vesicle: A membrane-bound particle released by cells that can transfer proteins, lipids and nucleic acids to distant cells, influencing tumour microenvironments.

References

1. Tumor-Intrinsic PD-L1 Signaling in Cancer Initiation, Development and Treatment: Beyond Immune Evasion. Frontiers in Oncology (2018).
2. Immune checkpoints between epithelial-mesenchymal transition and autophagy: A conflicting triangle. Cancer Letters (2024).
3. Proximity proteome mapping reveals PD-L1-dependent pathways disrupted by anti-PD-L1 antibody specifically in EGFR-mutant lung cancer cells. Cell Communication and Signaling (2023).
4. Engineering high‐affinity dual targeting cellular nanovesicles for optimised cancer immunotherapy. Journal of Extracellular Vesicles (2023).