Pdl1 Tests: Purpose, Test Details & Results

Purpose of Pdl1 Tests

Understanding why PD-L1 tests are performed is crucial for anyone facing cancer diagnosis and treatment decisions. At their core, PD-L1 (programmed death-ligand 1) tests are designed to identify which patients are most likely to benefit from cutting-edge immunotherapies—drugs that harness the body’s immune system to fight cancer. By measuring PD-L1 expression in tumors, clinicians can make more informed choices about treatment options, potentially improving outcomes for patients across a variety of cancer types.

Why Test for PD-L1?

PD-L1 is a protein expressed on the surface of some cancer cells and immune cells. Its main biological function is to suppress immune responses, which tumors exploit to avoid being attacked by the body’s immune system. By detecting PD-L1, clinicians can:

• Predict Response to Immunotherapy: Certain immunotherapy drugs (known as immune checkpoint inhibitors) specifically target the PD-1/PD-L1 interaction. High PD-L1 expression often indicates a higher chance of response to such treatments, especially in cancers like non-small cell lung cancer (NSCLC), melanoma, bladder cancer, and more 2 3 5 7.
• Select the Right Patients: Not everyone benefits from these expensive and potentially toxic therapies. PD-L1 testing helps identify patients most likely to respond, sparing others from unnecessary treatment 2 3.
• Support Clinical Trial Eligibility: Many clinical trials require PD-L1 testing to determine whether patients can enroll in studies of new immunotherapies 7.

The Expanding Role Across Cancer Types

Initially developed for lung cancer, PD-L1 testing now informs treatment in a range of malignancies, including:

• Non-Small Cell Lung Cancer (NSCLC)
• Bladder/Urothelial Cancer
• Gastric and Ovarian Cancers
• Hodgkin and B-cell Lymphomas
• Melanoma and others 2 4 6 7

Beyond Expression: PD-L1 Amplification

Emerging evidence suggests that not only protein expression but also genetic amplification of the PD-L1 gene (CD274) may predict benefit from immunotherapy, even when PD-L1 protein levels are low 8. This opens new avenues for using PD-L1 as a biomarker beyond its traditional role.

Pdl1 Tests Details

When your doctor orders a PD-L1 test, what exactly happens in the lab? Understanding the technical details can help demystify the process and highlight why results may vary. PD-L1 testing is most commonly performed using immunohistochemistry (IHC), a technique that uses antibodies to detect PD-L1 protein in tissue samples. However, there are several types of PD-L1 assays, each with its own nuances and implications for therapy.

Immunohistochemistry Assays: How They Work

• Sample Collection: Most often, a small piece of tumor tissue (biopsy) is obtained and processed.
• Staining Process: Specific antibodies (e.g., 22C3, 28-8, SP142, SP263, E1L3N) are used to stain PD-L1 protein in the sample.
• Platform Differences: The staining is performed on automated platforms (e.g., Dako Link 48, Ventana Benchmark, Leica Bond). Each platform uses a specific antibody clone and protocol 1 6 7.
• Scoring: A pathologist examines the stained slides under a microscope and estimates the percentage of tumor and/or immune cells expressing PD-L1. Some assays focus on tumor cells alone; others include immune cells 1 2 7.

Major Approved Assays and Their Differences

• 22C3 and 28-8 (Dako): Widely used in lung cancer, with similar performance and scoring systems (tumor proportion score, TPS). Both are FDA-approved companion diagnostics for specific drugs 1 6.
• SP142 and SP263 (Ventana): Used for a range of solid tumors. SP142 is noted for lower sensitivity and tends to report lower PD-L1 expression compared to others 1 6. SP263 is used in some urothelial and lung cancer settings.
• E1L3N: Often used in research or laboratory-developed tests. Has shown comparable results to 28-8 in some settings 1 4.

Cutoff Points and Scoring Algorithms

• Cutoff Variability: There is no universal definition for what constitutes “positive” PD-L1 expression. Cutoffs may be 1%, 5%, 10%, or 50% depending on the cancer type, assay, and drug being considered 2 3 5 7.
• Scoring Systems: Common systems include Tumor Proportion Score (TPS), which measures the percentage of tumor cells staining for PD-L1, and Combined Positive Score (CPS), which includes both tumor and immune cells 6 7.

Validation and Concordance

• Inter-assay Variability: While many assays are analytically similar, some (like SP142) produce consistently lower results, and interchangeability remains a topic of debate 1 2 3 7.
• Pathologist Concordance: Studies show high agreement among pathologists when scoring tumor cells, but lower agreement for immune cell scoring 1 2.
• Quality Assurance: Regular validation, internal reviews, and participation in external quality assurance programs are recommended to ensure test accuracy 3 7.

Challenges and Pitfalls

• Pre-analytical Factors: The type of tissue, how it’s handled, and when it’s collected can all impact test results 3 5 7.
• Lack of Standardization: Different drugs require different tests and cutoffs, creating complexity and potential confusion in clinical decision-making 2 3 5.
• Interpretation Complexity: Not all “positive” results mean the same thing across cancers, drugs, and scoring systems 3 7.

Pdl1 Tests Results & Follow-Up

Once the PD-L1 test is complete, the results guide some of the most important decisions in cancer care. But what do these results actually mean, and what happens next? Let’s break down what to expect.

Interpreting the Results

PD-L1 results are typically reported as a percentage, reflecting the proportion of tumor (and sometimes immune) cells that express the protein:

• Negative: No or minimal PD-L1 expression (e.g., <1%). Suggests less chance of responding to immunotherapies targeting PD-1/PD-L1. However, some patients with negative results may still benefit, depending on other factors 3 6 7.
• Low Expression: Intermediate results (e.g., 1–49%). Some drugs and clinical trials allow treatment in this range, but expected benefit is lower than in high expressers 6 3 7.
• High Expression: High proportion of tumor or combined cells positive (e.g., ≥50%). These patients are most likely to benefit from immunotherapy, and treatment is often recommended 3 6 7 5.

Factors Influencing Results

• Tumor Type and Stage: The clinical significance of PD-L1 positivity varies by cancer type and treatment context 3 7.
• Assay Used: Different assays and scoring systems can yield different results from the same sample 1 3 7.
• Intra-tumor Heterogeneity: PD-L1 expression can vary within different areas of the same tumor or change over time 3 5 7.
• Genetic Amplification: Rarely, tumors show genetic amplification of the PD-L1 gene, which can be associated with response to immunotherapy even if protein expression is low 8.

What Happens After Receiving Results?

• Treatment Planning: Results are discussed in a multidisciplinary tumor board or with your oncologist to tailor the treatment plan.
• Immunotherapy Eligibility: High PD-L1 expression often means eligibility for first-line checkpoint inhibitor therapy; lower expression may necessitate combination strategies or alternative treatments 3 5 7.
• Clinical Trial Options: Some patients may be eligible for novel therapies or trials based on their PD-L1 status 7.
• Repeat Testing: If results are unclear or contradictory, repeat testing or a second opinion may be advised 1 2 3 7.

Limitations and Uncertainties

• Not a Perfect Predictor: While helpful, PD-L1 is an imperfect biomarker. Some patients with low or negative PD-L1 still respond to immunotherapy, and not all high expressers benefit 3 5 7.
• Evolving Science: As research progresses, new biomarkers and testing approaches will continue to refine and improve patient selection 3 5 8.

Conclusion

PD-L1 testing has become an essential component of modern cancer care, guiding the use of powerful immunotherapies that are changing outcomes for many patients. However, the science and practice of PD-L1 testing are complex, with multiple assays, scoring systems, and evolving guidelines.

Main points covered:

• Purpose: PD-L1 tests help identify patients most likely to benefit from immunotherapies, sparing others from unnecessary side effects and costs.
• Test Details: Multiple immunohistochemistry assays exist, each with unique protocols and cutoffs. Differences among assays, scoring, and tissue factors can affect results.
• Results & Follow-Up: PD-L1 results guide treatment planning, but interpretation requires expertise. High expression favors immunotherapy, but decisions must be individualized. Repeat or additional testing is sometimes needed.

As research continues and testing standards evolve, close collaboration between oncologists, pathologists, and patients will remain critical to maximizing the benefits of PD-L1 testing in the fight against cancer.