TY - JOUR
T1 - PD-L1 expression in melanoma
T2 - A quantitative immunohistochemical antibody comparison
AU - Sunshine, Joel C.
AU - Nguyen, Peter L.
AU - Kaunitz, Genevieve J.
AU - Cottrell, Tricia R.
AU - Berry, Sneha
AU - Esandrio, Jessica
AU - Xu, Haiying
AU - Ogurtsova, Aleksandra
AU - Bleich, Karen B.
AU - Cornish, Toby C.
AU - Lipson, Evan J.
AU - Anders, Robert A.
AU - Taube, Janis M.
N1 - Funding Information:
The authors would like to thank Dr. David Rimm at Yale University, and Hao Wang and Brandon Luber at Johns Hopkins University, for helpful discussions. This work was supported by the Bloomberg~Kimmel Institute for Cancer Immunotherapy (to J.M. Taube, E.J. Lipson, R.A. Anders), Dermatology Foundation (to J.M. Taube), WW. Smith Foundation (to J.M. Taube), Moving for Melanoma Delaware (to J.M. Taube, E.J. Lipson), NIH R01 CA142779 (to J.M. Taube), NIH T32 CA193145 (to T.R. Cottrell), and the Melanoma Research Alliance (to J.M. Taube, T.R. Cottrell). J.M. Taube and R.A. Anders were also supported by a Stand Up To Cancer—Cancer Research Institute Cancer Immunology Translational Cancer Research Grant (Grant No.: SU2C-AACR-DT1012). Stand Up To Cancer is a program of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the Scientific Partner of SU2C. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Funding Information:
The authors would like to thank Dr. David Rimm at Yale University, and Hao Wang and Brandon Luber at Johns Hopkins University, for helpful discussions. This work was supported by the Bloomberg~Kimmel Institute for Cancer Immunotherapy (to J.M. Taube, E.J. Lipson, R.A. Anders), Dermatology Foundation (to J.M. Taube), WW. Smith Foundation (to J.M. Taube), Moving for Melanoma Delaware (to J.M. Taube, E.J. Lipson), NIH R01 CA142779 (to J.M. Taube), NIH T32 CA193145 (to T.R. Cottrell), and the Melanoma Research Alliance (to J.M. Taube, T.R. Cottrell). J.M. Taube and R.A. Anders were also supported by a Stand Up To Cancer—Cancer Research Institute Cancer Immunology Translational Cancer Research Grant (Grant No.: SU2C-AACR-DT1012). Stand Up To Cancer is a program of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the Scientific Partner of SU2C.
Funding Information:
E.J. Lipson reports receiving commercial research grants from Genentech and is a consultant/advisory board member for Bristol-Myers Squibb, EMD Serono, Merck, and Novartis. J.M. Taube reports receiving commercial research grants from Bristol-Myers Squibb and is a consultant/advisory board member for AstraZeneca, Bristol-Myers Squibb, and Merck. No potential conflicts of interest were disclosed by the other authors.
Publisher Copyright:
©2017 AACR.
PY - 2017/8/15
Y1 - 2017/8/15
N2 - Purpose: 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. Experimental Design: 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/H-scores, were assessed for each melanoma specimen using a computer-assisted platform. Staining properties were compared between antibodies. Results: Strong correlations were observed between the percentage of PD-L1(þ) cells across all clones studied (R2 = 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/H-scores strongly correlated with percentage of PD-L1(þ) cells (R2 > 0.78, all clones). Conclusions: 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/H-score in chromogenic PD-L1 IHC assays.
AB - Purpose: 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. Experimental Design: 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/H-scores, were assessed for each melanoma specimen using a computer-assisted platform. Staining properties were compared between antibodies. Results: Strong correlations were observed between the percentage of PD-L1(þ) cells across all clones studied (R2 = 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/H-scores strongly correlated with percentage of PD-L1(þ) cells (R2 > 0.78, all clones). Conclusions: 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/H-score in chromogenic PD-L1 IHC assays.
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UR - http://www.scopus.com/inward/citedby.url?scp=85028074698&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-16-1821
DO - 10.1158/1078-0432.CCR-16-1821
M3 - Article
C2 - 28428193
AN - SCOPUS:85028074698
SN - 1078-0432
VL - 23
SP - 4938
EP - 4944
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 16
ER -