Why Should PD-L1 Be Tested？

The development and application of antibodies targeting PD-1 (nivolumab and pembrolizumab) and PD-L1 (atezolizumab, avelumab, and durvalumab) have yielded favourable therapeutic effects across various solid tumors, including lung cancer, melanoma, renal cell carcinoma, Hodgkin's lymphoma, urothelial cancer, head and neck cancer, gastric cancer, Merkel cell carcinoma, and mismatch repair-deficient or microsatellite instability-high solid tumors. Among the emerging immune-relevant biomarkers for anti-PD-1/PD-L1 immunotherapy, the expression of PD-L1 on tumor and immune cells is a plausible biomarkers, overexpressing PD-L1 on the one side is associated with worse prognosis in cancer patients and on the other hand is considered a biologically plausible and targetable available biomarker in predicting the tumor response and survival prognosis. 

The Importance of Quality Control in PD-L1 IHC Testing

PD-L1 exhibits membranous staining. However, a range of factors—including fixation, antigen retrieval, antibody clones, reaction time, temperature, and substrate concentration—can all influence PD-L1 staining intensity. Furthermore, the reporting of different cut-offs for defining positive and negative expression; compounded by the possibility of interlaboratory variation also compromise the accuracy of PD-L1 IHC results. Therefore, a pooled analysis is essential to clarify the utility of PD-L1 expression in predicting the efficacy of anti-PD-1/PD-L1 immunotherapy. On-slide positive and negative controls from the same institution or manufacturer should be used, especially if an automated stainer is not employed. 

References

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[2]. Teixidó C, Vilariño N, Reyes R, et al.PD-L1 expression testing in non-small cell lung cancer[J]. Ther Adv Med Oncol. 2018 Apr 11;10:1758835918763493.

[3]. Lopez-Beltran A, López-Rios F, Montironi R, et al.Immune Checkpoint Inhibitors in Urothelial Carcinoma: Recommendations for Practical Approaches to PD-L1 and Other Potential Predictive Biomarker Testing[J]. Cancers (Basel). 2021 Mar 20;13(6):1424.

[4]. Martinez-Morilla S, McGuire J, Gaule P, et al. Quantitative assessment of PD-L1 as an analyte in immunohistochemistry diagnostic assays using a standardized cell line tissue microarray[J]. Lab Invest. 2020 Jan;100(1):4-15.