PD-L1 Expression in Melanoma: A Quantitative Immunohistochemical Antibody Comparison.

Abstract

<b>Purpose:</b> PD-L1 expression in the pretreatment tumor microenvironment enriches for response to anti-PD-1/PD-L1 therapies. The purpose of this study was to quantitatively compare the performance of five monoclonal anti-PD-L1 antibodies used in recent landmark publications.<b>Experimental Design:</b> PD-L1 IHC was performed on 34 formalin-fixed paraffin-embedded archival melanoma samples using the 5H1, SP142, 28-8, 22C3, and SP263 clones. The percentage of total cells (including melanocytes and immune cells) demonstrating cell surface PD-L1 staining, as well as intensity measurements/<i>H</i>-scores, were assessed for each melanoma specimen using a computer-assisted platform. Staining properties were compared between antibodies.<b>Results:</b> Strong correlations were observed between the percentage of PD-L1(+) cells across all clones studied (<i>R</i>² = 0.81-0.96). When present, discordant results were attributable to geographic heterogeneity of the melanoma tissue section rather than differences in PD-L1 antibody staining characteristics. PD-L1 intensity/<i>H</i>-scores strongly correlated with percentage of PD-L1(+) cells (<i>R</i>² > 0.78, all clones).<b>Conclusions:</b> The 5H1, SP142, 28-8, 22C3, and SP263 clones all demonstrated similar performance characteristics when used in a standardized IHC assay on melanoma specimens. Reported differences in PD-L1 IHC assays using these antibodies are thus most likely due to assay characteristics beyond the antibody itself. Our findings also argue against the inclusion of an intensity/<i>H</i>-score in chromogenic PD-L1 IHC assays. <i>Clin Cancer Res; 23(16); 4938-44. ©2017 AACR</i>.