Abstract
Introduction
PD-L1 is established as a predictive marker for therapy of non-small cell lung cancer with pembrolizumab. Furthermore, PD-L1 positive melanoma has shown more favorable outcomes when treated with anti-PD1 antibodies and dacarbazine compared to PD-L1 negative melanoma. However, the role of PD-L1 expression with regard to response to checkpoint inhibition with anti-CTLA-4 is not clear, yet. In addition, the lack of standardization in the immunohistochemical assessment of PD-L1 makes the comparison of results difficult. In this study, we investigated the PD-L1 gene expression with a new fully automated technique via RT-PCR and correlated the findings with the response to the anti-CTLA-4 antibody ipilimumab.
Materials and methods
Within a retrospective multi-center trial, PD-L1 gene expression was evaluated in 78 melanoma patients in a total of 111 pre-treatment tumor samples from 6 skin cancer centers and analyzed with regard to response to ipilimumab. For meaningful statistical analysis, the cohort was enriched for responders with 30 responders and 48 non-responders. Gene expression was assessed by quantitative RT-PCR after extracting mRNA from formalin-fixed paraffin embedded tumor tissue and correlated with results from immunohistochemical (IHC) stainings.
Results and discussion
The evaluation of PD-L1 expression based on mRNA level is feasible. Correlation between PD-L1 expression as assessed by IHC and RT-PCR showed varying levels of concordance depending on the antibody employed. RT-PCR should be further investigated to measure PD-L1 expression, since it is a semi-quantitative method with observer-independent evaluation. With this approach, there was no statistical significant difference in the PD-L1 expression between responders and non-responders to the therapy with ipilimumab. The evaluation of PD-L1 expression based on mRNA level is feasible. Correlation between PD-L1 expression as assessed by IHC and RT-PCR showed varying levels of concordance depending on the antibody employed. RT-PCR should be further investigated to measure PD-L1 expression, since it is a semi-quantitative method with observer-independent evaluation. With this approach, there was no statistical significant difference in the PD-L1 expression between responders and non-responders to the therapy with ipilimumab.
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Acknowledgements
The present work was performed in the fulfillment of the requirements for obtaining the degree ‘‘Dr. med.’’. We thank all patients and their relatives.
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The study was approved by the local ethics committee of the University Erlangen.
Conflict of interest
BW received research founding and honoraria from Bristol-Myers Squibb (BMS). SG is a member of a BMS advisory board and received honoraria and a travel grant from BMS and Merck Sharp and Dohme (MSD). DS receives research funding from Bristol-Myers Squibb and has a consultant or advisory board relationship with BMS. RC is a member of a Sysmex Corporation advisory board. CH received honoraria, and travel grants from BMS. He was also a member of a BMS advisory board. RD receives research funding from BMS and has a consultant or advisory board relationship with BMS. MS obtained funding from Siemens Healthcare Diagnostics GmbH and a research Grant for colorectal carcinoma from Siemens Healthcare Diagnostics. This is not in conflict with the present study and did not affect the interpretation of the results of the present studies. LH is a member of a BMS advisory board and of the former ipilimumab reference center. She has also received travel grants from BMS. KCK is a member of a BMS advisory board and of the former ipilimumab reference center. All the remaining authors have declared no conflicts of interest.
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Brüggemann, C., Kirchberger, M.C., Goldinger, S.M. et al. Predictive value of PD-L1 based on mRNA level in the treatment of stage IV melanoma with ipilimumab. J Cancer Res Clin Oncol 143, 1977–1984 (2017). https://doi.org/10.1007/s00432-017-2450-2
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DOI: https://doi.org/10.1007/s00432-017-2450-2