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PD-L1 Testing in Guiding Patient Selection for PD-1/PD-L1 Inhibitor Therapy in Lung Cancer

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Abstract

Immunotherapy with programmed death 1 (PD-1)- and programmed death-ligand 1 (PD-L1)-targeted monoclonal antibodies has dramatically changed the therapeutic and prognostic landscape for several types of malignancy. PD-1 and PD-L1 are immune checkpoint proteins whose binding ultimately result in T cell exhaustion and self-tolerance. Blocking this pathway ‘releases the brakes’ on the immune system and allows for attack of tumor cells that express PD-L1. The clinical trials that led to the US Food and Drug Administration (FDA) approval of these agents used different immunohistochemical (IHC) platforms with various PD-L1 antibodies to assess for PD-L1 expression on either tumor cells or tumor-infiltrating immune cells. There are four PD-L1 IHC assays registered with the FDA, using four different PD-L1 antibodies (22C3, 28-8, SP263, SP142), on two different IHC platforms (Dako and Ventana), each with their own scoring systems. Attempts at harmonization of PD-L1 IHC antibodies and staining platforms are underway. While PD-L1 IHC can be used to predict the likelihood of response to anti-PD-1 or anti-PD-L1 therapy, a proportion of patients that are negative can have a response and identification of alternative biomarkers is critical to further refine selection of patients most likely to respond to these therapies.

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Correspondence to Liza C. Villaruz.

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No funding was received for the preparation of this manuscript.

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Mark Socinski has received consulting fees or honorarium, and payment for lectures including service on speaker bureaus from Bristol-Meyers Squibb and Genentech. Katerina Ancevski Hunter and Liza Villaruz declare no conflict of interest.

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Ancevski Hunter, K., Socinski, M.A. & Villaruz, L.C. PD-L1 Testing in Guiding Patient Selection for PD-1/PD-L1 Inhibitor Therapy in Lung Cancer. Mol Diagn Ther 22, 1–10 (2018). https://doi.org/10.1007/s40291-017-0308-6

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