PD-L1 Immunohistochemistry in Lung Cancer Diagnostics

Programmed death ligand 1 (PD-L1) immunohistochemistry has become a cornerstone in the diagnostic pathway of non-small cell lung cancer (NSCLC), guiding the use of anti-PD-1/PD-L1 therapies. By visualising PD-L1 protein expression on tumour cells and associated immune infiltrates, pathologists can stratify patients for checkpoint inhibitor treatment. Standardised assays employ monoclonal antibodies to detect membranous PD-L1, with results reported as a percentage of positive tumour cells or as a combined score of tumour and immune cell staining. These results inform clinical decisions, including the eligibility threshold for first-line pembrolizumab or combination regimens. Despite the clear clinical utility, practical challenges remain: heterogeneity of PD-L1 expression within and between lesions, variability among companion diagnostic platforms, and inter-observer scoring differences. Advances in assay development, digital image analysis and quantitative methods aim to enhance reproducibility. Moreover, harmonisation efforts seek to align cut-off values across antibody clones and platforms. The precise assessment of PD-L1 by immunohistochemistry is thus integral to precision oncology, demanding robust protocols and experienced interpretation to optimise patient outcomes.

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PD-L1 Immunohistochemistry in Lung Cancer Diagnostics publication trend

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

Technical terms

PD-L1: A transmembrane protein on tumour and immune cells that binds PD-1 to inhibit T-cell activity, serving as a predictive biomarker for checkpoint blockade therapies.

Immunohistochemistry (IHC): A staining technique using specific antibodies to visualise protein expression in formalin-fixed, paraffin-embedded tissue sections.

Companion diagnostic: A laboratory test approved alongside a targeted therapy to identify patients most likely to benefit from that treatment.

Tumour proportion score (TPS): The percentage of viable tumour cells exhibiting membranous PD-L1 staining at any intensity, used to guide treatment eligibility.

Combined positive score (CPS): The ratio of PD-L1–positive cells (tumour and immune) to total viable tumour cells, expressed per 100 cells, employed in certain tumour types.

Heterogeneity: Variability in biomarker expression within different regions of the same tumour or between primary and metastatic sites, which may affect diagnostic accuracy.

References

1. Heterogeneity of PD-L1 expression in non-small cell lung cancer: Implications for specimen sampling in predicting treatment response. Lung Cancer (2019).
2. “Interchangeability” of PD-L1 immunohistochemistry assays: a meta-analysis of diagnostic accuracy. Modern Pathology (2019).
3. Quantitative and qualitative characterization of Two PD-L1 clones: SP263 and E1L3N. Diagnostic Pathology (2016).