Programmed Death-Ligand 1 Expression in Non-Small Cell Lung Cancer

Programmed death-ligand 1 (PD-L1) is a cell surface protein that binds to the programmed cell death protein 1 (PD-1) receptor on T lymphocytes, acting as a critical checkpoint in immune tolerance. In non-small cell lung cancer (NSCLC), PD-L1 expression varies widely among histological subtypes and stages, reflecting complex interactions between oncogenic drivers, inflammatory cytokines and the tumour microenvironment. Measurement of PD-L1 by immunohistochemistry has become central to clinical practice, guiding the use of PD-1/PD-L1-blocking antibodies, which have transformed outcomes for a subset of patients with advanced disease. Expression thresholds, commonly expressed as tumour proportion scores, inform treatment selection and may predict response durability. However, assay variability and intratumoural heterogeneity remain challenges to standardisation. Beyond its predictive value, PD-L1 has been investigated as a prognostic marker, with elevated levels often correlating with aggressive features and poorer survival, though this association can differ by tumour subtype and therapeutic context. Ongoing global efforts aim to integrate PD-L1 assessment with other biomarkers, refine companion diagnostics and develop combination strategies to overcome resistance, thereby maximising the clinical benefit of immune checkpoint blockade in NSCLC.

Research from Nature Portfolio

Recent studies have elucidated how treatment modalities modulate PD-L1 and its interplay with other immune checkpoints. An analysis of patients receiving preoperative concurrent chemo-radiotherapy demonstrated a substantial increase in PD-L1 expression compared with those receiving drug therapy alone, and identified a concurrent rise in TIGIT that correlated with poorer prognosis, highlighting the rationale for combined targeting of PD-L1 and TIGIT. A comprehensive meta-analysis across diverse cohorts established that high PD-L1 expression is associated with reduced overall survival in NSCLC and identified links with clinicopathological factors such as gender, smoking history, tumour differentiation and specific genetic alterations, thereby providing a robust prognostic framework for PD-L1 evaluation in clinical practice.

Programmed Death-Ligand 1 Expression in Non-Small Cell Lung Cancer publication trend

The graph below shows the total number of articles in programmed death-ligand 1 expression in non-small cell lung cancer across all publications each year (not limited to Nature Index journals).

Technical terms

PD-L1: Programmed death-ligand 1, an immune-checkpoint protein on tumour and immune cells that inhibits T cell activity.

PD-1: Programmed cell death protein 1, a receptor on T lymphocytes that mediates suppression of immune responses upon binding PD-L1.

NSCLC: Non-small cell lung cancer, comprising the majority of lung tumours and including adenocarcinoma and squamous cell carcinoma.

Immunohistochemistry: A laboratory technique using antigen-specific antibodies to detect proteins in tissue sections.

Tumour proportion score: The percentage of viable tumour cells showing PD-L1 membrane staining, used to quantify expression.

TIGIT: T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain, a co-inhibitory receptor that can collaborate with PD-L1 to dampen antitumour immunity.

References

1. Prognostic impact of PD-L1 and TIGIT expression in non-small cell lung cancer following concurrent chemo-radiotherapy. Scientific Reports (2023).
2. PD-L1 expression in lung cancer and its correlation with driver mutations: a meta-analysis. Scientific Reports (2017).
3. Evaluation of the Prognostic Impact of SP263-Evaluated PD-L1 Expression in Patients with Stage III Non-Small Cell Lung Cancer (NSLC) Treated with Radio-Chemotherapy. Biomedicines (2024).
4. High expression of PD-L1 mainly occurs in non-small cell lung cancer patients with squamous cell carcinoma or poor differentiation. Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics (2023).