Muhammad Vohra

Introduction. Non-Small Cell Lung Carcinoma (NSCLC) is a type of lung cancer that originates from epithelial lung cells and is responsible for 85% of all lung cancers.[1] Programmed death ligand 1(PD-L1), a member of the CD28 family, is a key immune checkpoint receptor expressing on the surface of activated T, B and NK cells which plays a crucial role in tumor mediated immune escape.[2] NSCLC tumor variability in PD-L1 expression is directly linked to the effectiveness of monoclonal anti-PDL1 antibodies.[3] Immunohistochemistry (IHC) is primarily used in detecting PD-L1 expression in NSCLC tumor cells. This method is problematic due to the lack of standardization and the possibility of heterogenous expression of PD-L1.[4]  PD-L1 expression is directly linked with greater survival rates and the effectiveness of monoclonal antibodies.[5] Methods. 22 NSCLC cases including mediastinal lymph node biopsies were evaluated for PD-L1 protein on tumor and immune cells and PD-L1 mRNA using the CheckPoint Typer assay.6] The impact of various PD-L1 expression rates on prognostic prediction in 321 patients whose NSCLC was evaluated with the use of immunohistochemistry.[5] Results. PD-L1 mRNA and IHC biomarker extraction data showed that there was agreement in the positive results. PD-L1 expression was positively detected in >50% of 28-8 IHC, and was reliable with the use of RT-qPCR.[6] PD-L1 expression on tumor cells was also associated with greater survivability in pulmonary squamous cell carcinomas.[5] Conclusions. PD-L1 expression on NSCLC cells as a predictive biomarker has utility to be used for prognostics and antibody treatment. The level of expression of PD-L1 and the survivability of the patient are related. The use of IHC in determining PD-L1 expression is problematic due to the lack of standardization. PD-L1 mRNA expression should be discussed as a possible alternative to this issue.

1. Zappa, Cecilia, and Shaker A. Mousa. “Non-Small Cell Lung Cancer: Current Treatment and Future ” Translational Lung Cancer Research 5, no. 3 (June 2016): 288–300.   https://doi.org/10.21037/tlcr.2016.06.07.
2. Teixidó, Cristina, Noelia Vilariño, Roxana Reyes, and Noemí Reguart. “PD-L1 Expression Testing in Non-Small Cell Lung Cancer.” Therapeutic Advances in Medical Oncology 10 (April 11, 2018). https://doi.org/10.1177/1758835918763493.
3. Gandhi, Leena, Ani Balmanoukian, Rina Hui, Omid Hamid, Naiyer A. Rizvi, Natasha Leighl, Matthew Gubens, et al. “Abstract CT105: MK-3475 (Anti-PD-1 Monoclonal Antibody) for Non-Small Cell Lung Cancer (NSCLC): Antitumor Activity and Association with Tumor PD-L1 Expression.” Cancer Research 74, no. 19 Supplement (October 1, 2014): CT105–CT105. https://doi.org/10.1158/1538-7445.AM2014-CT105.
4. Kerr, Keith M., Ming-Sound Tsao, Andrew G. Nicholson, Yasushi Yatabe, Ignacio I. Wistuba, and Fred R. Hirsch. “Programmed Death-Ligand 1 Immunohistochemistry in Lung Cancer: In What State Is This Art?” Journal of Thoracic Oncology 10, no. 7 (July 2015): 985–89. https://doi.org/10.1097/JTO.0000000000000526.
5. Schmidt, Lars Henning, Andreas Kümmel, Dennis Görlich, Michael Mohr, Sebastian Bröckling, Jan Henrik Mikesch, Inga Grünewald, et al. “PD-1 and PD-L1 Expression in NSCLC Indicate a Favorable Prognosis in Defined Subgroups.” PLoS ONE 10, no. 8 (August 27, 2015). https://doi.org/10.1371/journal.pone.0136023.
6. Erber, Ramona, Robert Stöhr, Stefanie Herlein, Claudia Giedl, Ralf Joachim Rieker, Florian Fuchs, Joachim H. Ficker, et al. “Comparison of PD-L1 MRNA Expression Measured with the CheckPoint Typer® Assay with PD-L1 Protein Expression Assessed with Immunohistochemistry in Non-Small Cell Lung Cancer.” Anticancer Research 37, no. 12 (2017): 6771–78. https://doi.org/10.2873/anticanres.12137.