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Programmed death-ligand 1 (PD-L1) is an immune-related biomarker that can be expressed on the surface of many tissue types, including tumor cells. For certain types and stages of cancer, testing for PD-L1 expression may help to identify patients most likely to benefit from treatment with PD-1 inhibitors. Novel immunotherapies, known as immune checkpoint inhibitors, can interrupt signals generated by immune checkpoint proteins, such as PD-L1, and can enhance antitumor T-cell immunity. , Several immune checkpoint inhibitors, including pembrolizumab, nivolumab, ipilimumab, and others, have been approved for a number of clinical indications and are being evaluated in multiple malignancies. The FDA divides PD-L1 immunohistochemistry (IHC) tests into two groups: companion diagnostic tests, which provide information that is essential for the safe and effective use of a drug (test results are required for drug use), and complementary or codiagnostic tests, which may be used in treatment selection but are not considered essential for use of the corresponding therapy (test results are NOT required for drug use). ,
Quick Answers for Clinicians
COMPANION programmed death-ligand 1 (PD-L1) testing is shown to be predictive of patient response to a specific immunotherapy for a type of tumor, on a specific platform. Testing is required for the specific immunotherapy to be used. COMPLEMENTARY PD-L1 testing may be predictive of patient response to a specific immunotherapy for a type of tumor, but this testing is not required to use immunotherapy.
Indications for Testing
PD-L1 testing may be considered for patients with specific types of malignancies to predict response to specific immune checkpoint inhibitors.
PD-L1 Laboratory Testing
PD-L1 testing recommendations depend on the drug being considered, the malignancy, and the stage of cancer. The FDA provides a list of cleared or approved companion diagnostic devices, including PD-L1 tests, with their indications.
PD-L1 Testing Interpretive Scoring Systems
There are several interpretive scoring systems available for PD-L1 testing, including the tumor proportion score (TPS), the combined positive score (CPS), and tumor-infiltrating immune cell (IC) staining assessments.
In brief, the TPS is based on the proportion of tumor cells that express PD-L1 to the total number of viable tumor cells (staining and nonstaining). The CPS is calculated in a manner similar to that used for the TPS, but the CPS includes PD-L1 expression in tumor-associated lymphocytes and macrophages in addition to the ratio of PD-L1-expressing tumor cells. For the 22C3 assay, either TPS or CPS can be used. For the 28-8 assay, TPS can be used.
The selection of which scoring system to use, as well as the interpretive cutoffs, depends on the test, tumor, and indications.
ARUP Laboratory Tests
Immunohistochemistry (IHC)
Immunohistochemistry (IHC)
References
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Massard C, Gordon MS, Sharma S, et al. Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer. J Clin Oncol. 2016;34(26):3119-3125.
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Udall M, Rizzo M, Kenny J, et al. PD-L1 diagnostic tests: a systematic literature review of scoring algorithms and test-validation metrics. Diagn Pathol. 2018;13(1):12.
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USFDA - Medical Devices: In Vitro Diagnostics
U.S. Food and Drug Administration. Medical devices: in vitro diagnostics. Last updated Dec 2018; accessed May 2023.
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FDA - list of cleared-approved companion diagnostic devises
U.S. Food and Drug Administration. List of cleared or approved companion diagnostic devices (in vitro and imaging tools). Updated Oct 2024; accessed Nov 2024.
PD-L1 scoring and interpretation (with CPS or TPS) will be provided based on tumor type and origin as determined by an ARUP pathologist. Refer to the ARUP Consult PD-L1 by Immunohistochemistry Test Fact Sheet for more information about ARUP’s PD-L1 test offerings.