Mini-Review Article

Status of Programmed Death Ligand 1 (PD-L1) by Immunohistochemistry and Scoring Algorithms

Author(s): Francesca Giunchi, Thomas Gevaert, Marina Scarpelli and Michelangelo Fiorentino*

Volume 21, Issue 13, 2020

Page: [1286 - 1292] Pages: 7

DOI: 10.2174/1389450121666200123124642

Price: $65


The detection of the Programmed Death Ligand 1 (PD-L1) protein by immunohistochemistry is currently the only approved test predictive of response to drugs targeting the PD1/PDL1 axis. The role of this test is debated since several reagents have been used as companion diagnostics for different drugs on diverse immunostaining platforms. In addition, different scoring systems for PD-L1 immunohistochemistry have been applied in the registration studies regarding single drugs. This review deals with the various issues that are related to the immunohistochemical test for PD-L1. We discuss currently unsolved problems such as the advantages and the flaws of PD-L1 immunohistochemistry; the choice of the best reagents and the best scoring system. Finally, we review the current experiences on the role of immunohistochemistry for PD-L1 in clinical trials with immune checkpoint inhibitors.

Keywords: Cancer, immunotherapy, PD-L1, immunohistochemistry, scoring systems, algorithms.

Graphical Abstract
Sharpe AH, Pauken KE. The diverse functions of the PD1 inhibitory pathway. Nat Rev Immunol 2018; 18(3): 153-67.
[] [PMID: 28990585]
Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012; 12(4): 252-64.
[] [PMID: 22437870]
Patel SP, Kurzrock R. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther 2015; 14(4): 847-56.
[] [PMID: 25695955]
Morgensztern D. KEYNOTE-042 and the role for single agent pembrolizumab in patients with PD-L1 tumor proportion score 1-49. J Thorac Dis 2019; 11(Suppl. 15): S1963-5.
[] [PMID: 31632798]
Shafique MR, Robinson LA, Antonia S. Durvalumab: a potential maintenance therapy in surgery-ineligible non-small-cell lung cancer. Cancer Manag Res 2018; 10: 931-40.
[] [PMID: 29760563]
Solinas C, Pusole G, Demurtas L, et al. Tumor infiltrating lymphocytes in gastrointestinal tumors: Controversies and future clinical implications. Crit Rev Oncol Hematol 2017; 110: 106-16.
[] [PMID: 28109400]
Pérottet J, Le Goff E, Legoupil D, et al. PD-L1 copy number variation does not correlate with pd-l1 expression or response to anti-pd-1 immunotherapy in patients with advanced melanomas. Appl Immunohistochem Mol Morphol IN PRESS
[] [PMID: 31335487]
Erlmeier F, Weichert W, Schrader AJ, et al. Prognostic impact of PD-1 and its ligands in renal cell carcinoma. Med Oncol 2017; 34(6): 99.
[] [PMID: 28432616]
Hellmann MD, Ciuleanu TE, Pluzanski A, et al. Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. N Engl J Med 2018; 378(22): 2093-104.
[] [PMID: 29658845]
Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012; 366(26): 2455-65.
[] [PMID: 22658128]
Straub M, Drecoll E, Pfarr N, et al. CD274/PD-L1 gene amplification and PD-L1 protein expression are common events in squamous cell carcinoma of the oral cavity. Oncotarget 2016; 7(11): 12024-34.
[] [PMID: 26918453]
Barlesi F, Vansteenkiste J, Spigel D, et al. Avelumab versus docetaxel in patients with platinum-treated advanced non-small-cell lung cancer (JAVELIN Lung 200): an open-label, randomised, phase 3 study. Lancet Oncol 2018; 19(11): 1468-79.
[] [PMID: 30262187]
Dirix LY, Takacs I, Jerusalem G, et al. Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study. Breast Cancer Res Treat 2018; 167(3): 671-86.
[] [PMID: 29063313]
Hirsch FR, McElhinny A, Stanforth D, et al. PD-L1 Immunohistochemistry assays for lung cancer: results from phase 1 of the Blueprint PD-L1 IHC assay comparison project. J Thorac Oncol 2017; 12(2): 208-22.
[] [PMID: 27913228]
Ratcliffe MJ, Sharpe A, Midha A, et al. Agreement between programmed cell death ligand-1 diagnostic assays across multiple protein expression cutoffs in non-small cell lung cancer. Clin Cancer Res 2017; 23(14): 3585-91.
[] [PMID: 28073845]
Giunchi F, Degiovanni A, Daddi N, et al. Fading with time of pd-l1 immunoreactivity in non-small cells lung cancer tissues: a methodological study. Appl Immunohistochem Mol Morphol 2018; 26(7): 489-94.
[] [PMID: 27801735]
Capizzi E, Ricci C, Giunchi F, et al. Validation of the immunohistochemical expression of programmed death ligand 1 (PD-L1) on cytological smears in advanced non small cell lung cancer. Lung Cancer 2018; 126: 9-14.
[] [PMID: 30527198]
Skov BG, Skov T. Paired comparison of PD-L1 expression on cytologic and histologic specimens from malignancies in the lung assessed with PD-L1 IHC 28-8pharmDx and PD-L1 IHC 22C3pharmDx. Appl Immunohistochem Mol Morphol 2017; 25(7): 453-9.
[] [PMID: 28549039]
She L, Hu H, Liao M, et al. Cost-effectiveness analysis of pembrolizumab versus chemotherapy as first-line treatment in locally advanced or metastatic non-small cell lung cancer with PD-L1 tumor proportion score 1% or greater. Lung Cancer 2019; 138: 88-94.
[] [PMID: 31655368]
Kulangara K, Zhang N, Corigliano E, et al. Clinical Utility of the Combined Positive Score for Programmed Death Ligand-1 Expression and the Approval of Pembrolizumab for Treatment of Gastric Cancer. Arch Pathol Lab Med 2019; 143(3): 330-7.
[] [PMID: 30028179]
Bellmunt J, Mullane SA, Werner L, et al. Association of PD-L1 expression on tumor-infiltrating mononuclear cells and overall survival in patients with urothelial carcinoma. Ann Oncol 2015; 26(4): 812-7.
[] [PMID: 25600565]
Nakanishi J, Wada Y, Matsumoto K, Azuma M, Kikuchi K, Ueda S. Overexpression of B7-H1 (PD-L1) significantly associates with tumor grade and postoperative prognosis in human urothelial cancers. Cancer Immunol Immunother 2007; 56(8): 1173-82.
[] [PMID: 17186290]
Massard C, Gordon MS, Sharma S, et al. Safety and efficacy of durvalumab (medi4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer. J Clin Oncol 2016; 34(26): 3119-25.
[] [PMID: 27269937]
Plimack ER, Bellmunt J, Gupta S, et al. Safety and activity of pembrolizumab in patients with locally advanced or metastatic urothelial cancer (KEYNOTE-012): a non-randomised, open-label, phase 1b study. Lancet Oncol 2017; 18(2): 212-20.
[] [PMID: 28081914]
Hodgson A, Slodkowska E, Jungbluth A, et al. PD-L1 immunohistochemistry assay concordance in urothelial carcinoma of the bladder and hypopharyngeal squamous cell carcinoma. Am J Surg Pathol 2018; 42(8): 1059-66.
[] [PMID: 29750666]
Rijnders M, van der Veldt AAM, Zuiverloon TCM, et al. PD-L1 Antibody Comparison in Urothelial Carcinoma. Eur Urol 2019; 75(3): 538-40.
[] [PMID: 30497882]
Reis H, Serrette R, Posada J, et al. PD-L1 expression in urothelial carcinoma with predominant or pure variant histology: concordance among 3 commonly used and commercially available antibodies. Am J Surg Pathol 2019; 43(7): 920-7.
[] [PMID: 31135485]
Powles T, Durán I, van der Heijden MS, et al. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial. Lancet 2018; 391(10122): 748-57.
[] [PMID: 29268948]
Choueiri TK, Fay AP, Gray KP, et al. PD-L1 expression in nonclear-cell renal cell carcinoma. Ann Oncol 2014; 25(11): 2178-84.
[] [PMID: 25193987]
Choueiri TK, Figueroa DJ, Fay AP, et al. Correlation of PD-L1 tumor expression and treatment outcomes in patients with renal cell carcinoma receiving sunitinib or pazopanib: results from COMPARZ, a randomized controlled trial. Clin Cancer Res 2015; 21(5): 1071-7.
[] [PMID: 25538263]
McDermott DF, Sosman JA, Sznol M, et al. Atezolizumab, an anti-programmed death-ligand 1 antibody, in metastatic renal cell carcinoma: long-term safety, clinical activity, and immune correlates from a phase ia study. J Clin Oncol 2016; 34(8): 833-42.
[] [PMID: 26755520]
Motzer RJ, Rini BI, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial. Lancet Oncol 2019; 20(10): 1370-85.
[] [PMID: 31427204]
Cocks M, Taheri D, Ball MW, et al. Immune-checkpoint status in penile squamous cell carcinoma: a North American cohort. Hum Pathol 2017; 59: 55-61.
[] [PMID: 27663086]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy