Blockade of the immune checkpoint programmed death receptor ligand-1 (PD-L1)/PD-1 pathway has well-established clinical activity across many tumor types. PD-L1 protein expression by immunohistochemistry is emerging as a predictive biomarker of response to these therapies. Here, we examine PD-L1 expression in a thymic epithelial tumor (TET) tissue microarray (TMA).
Methods
The TMA contained 69 TETs and 17 thymic controls, with each case represented by triplicate cores. The TMA was stained with rabbit monoclonal antibody (clone 15; Sino Biological, Beijing, China) to human PD-L1. PD-L1 staining was scored based on intensity as follows: 0 = none, 1 = equivocal/uninterpretable, 2 = weak, and 3 = intermediate-strong. Those cases with all cores scoring three in the epithelial component were categorized as PD-L1high and the remaining as PD-L1low.
Results
PD-L1high scores were more frequent in TETs than in controls (68.1% versus 17.6%; p = 0.0036). PD-L1 scores and histology were significantly correlated, with higher intensity staining in World Health Organization (WHO). B2/B3/C TETs. Only 14.8% of TETs had PD-L1 staining of associated lymphocytes. In an adjusted analysis (age/sex), PD-L1high TETs had a significantly worse overall survival (hazard ratio: 5.40, 95% confidence interval: 1.13–25.89; p = 0.035) and a trend for worse event-free survival (hazard ratio: 2.94, 95% confidence interval: 0.94–9.24; p = 0.064).
Conclusions
PD-L1 expression was present in all cases of TETs within the epithelial component but only in a minority in the lymphocytic component. TETs stained more intensely for PD-L1 than in controls, and PD-L1high TETs were associated with more aggressive histology and worse prognosis. This study lends rationale to a clinical trial with anti-PD-1/PD-L1 therapy in this rare tumor type.
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Disclosure: Heather A. Wakelee: No disclosures in relation to this submitted work. Disclosures outside the submitted work include consultancy to Peregrine (money paid to author) and grants from Celgene, Genentech/Roche, Lilly, Pfizer, MedImmune, AstraZeneca, Novartis, BMS, Clovis, Exelixis, Regeneron, Xcovery (money paid to institution). Joel W. Neal: No disclosures in relation to this submitted work. Disclosures outside of the submitted work include grants paid to author and/or institution (Merck, ArQule, Genentech/Roche). Jonathan W. Riess: No disclosures in relation to this submitted work. Disclosures outside this submitted work include Celgene (consulting), Genentech/Roche (honoraria), research funding paid to institution (Novartis, Onconova, Millennium).
