PD-L1 Is an Independent Prognostic Marker in Middle Eastern PTC and Its Expression Is Upregulated by Mutation.

PD-L1 inhibition is a promising therapeutic target whose efficacy has been demonstrated in several cancers. Immunohistochemistry was performed to assess PD-L1 protein expression in PTC. We further conducted in vitro analysis to investigate the role of PD-L1 in regulating in PTC cell lines. PD-L1 over-expression was noted in 32.4% (473/1458) of cases and significantly associated with aggressive clinico-pathological parameters. Importantly, PD-L1 was found to be an independent poorer prognostic marker. We also found PD-L1 to be significantly associated with mutation and patients with co-existing PD-L1 over-expression and mutation had a poor disease-free survival compared to patients with mutation alone. In vitro analysis showed high expression of PD-L1 in -mutated PTC cell lines compared to a wild-type cell line. Inhibition of BRAF using vemurafenib induced PD-L1 expression in -mutated cell lines without affecting cell growth. Knockdown of PD-L1 in -mutated cell lines significantly decreased the cell growth and induced apoptosis. Our data suggest that PD-L1 might represent a useful prognostic marker in Middle Eastern PTC and PD-L1 inhibition could be a potential therapeutic option for aggressive PTC cancers, such as the tall cell variant, mutation-positive patients that are unresponsive to standard treatment.