- Also Known As:
- Programmed Cell Death -Ligand 1 (PD-L1)
- Immune Checkpoint Inhibitor
- Formal Name:
- Programmed Death-Ligand 1 (PD-L1) Immunohistochemistry
At a Glance
Why Get Tested?
To help guide treatment of non-small cell lung cancer or several other cancers
When To Get Tested?
When you have been diagnosed with non-small cell lung cancer, or another cancer; when you are being treated, but the cancer progresses
A sample of cancer cells from a biopsy or from the surgical removal of cancerous tissue
Test Preparation Needed?
In many cases preparation is minimal, but it will depend upon how the cancer cells are collected. You will receive instructions from your health care practitioner based on the procedure being used to obtain the sample.
What is being tested?
Programmed Death-Ligand 1 (PD-L1) is a protein that can be found on the surface of many cells throughout the body. Some, but not all, tumor cells have large amounts of PD-L1 that help the tumor cells evade the body’s natural defense system—the immune system. A lab test measures how much PD-L1 is present on tumor cells, which can help guide treatment of certain cancers.
One of the ways our immune system fights diseases like cancer is with T cells (T lymphocytes), a type of white blood cell. Some types of T-cells recognize and directly attack cancer cells as well as some other abnormal or infected cells. However, the body has “immune checkpoints,” which prevent T-cells from attacking normal cells. PD-L1 and another protein called PD-1 (Programmed Death-1) are part of an immune checkpoint. PD-L1 on the body’s normal cells recognizes and attaches to PD-1 on T cells, turning off (inactivating) the T cell so it can’t attack cells.
However, some tumor cells have large amounts of PD-L1. This is a problem because it helps protect the cancer from being attacked by T cells. The cancer cells are more likely to inactivate T cells, escape immune system action, and survive.
New cancer drugs (immunotherapies) have been developed to disrupt the interaction between PD-L1 and PD-1. These immunotherapies are antibodies that attach to PD-L1 or PD-1 and block their interaction so that T cells are not inactivated by cancer cells. This boosts the body’s natural immune system and its ability to recognize and fight the cancer.
Blocking this immune checkpoint pathway with PD-1 and PD-L1 antibodies has stopped or slowed the growth of cancers such as melanoma, non-small cell lung cancer, kidney cancer, bladder cancer, head and neck cancers, and Hodgkin lymphoma. These immunotherapies are also being studied for treatment of many other types of cancer.
How is the test used?
This test is used to detect PD-L1 in tumor tissue to help guide treatment of some cancers, such as non-small cell lung cancer or several other cancers. Knowing whether PD-L1 is present on the cells can help determine if immunotherapy (PD-1 or PD-L1 inhibitors), such as atezolizumab, nivolumab, and pembrolizumab, may be beneficial for treating the tumor.
Tissue from a tumor may be tested for PD-L1 using immunohistochemistry (IHC) to determine if there is a sufficient amount of PD-L1 present to make you a good candidate for inhibitor therapy.
PD-L1 test variations
There are several variations of the PD-L1 test, and they are not interchangeable. Tests and test interpretation “scoring” types are matched up both with the kind of cancer you have and the specific immunotherapy drug that your health care practitioner is considering.
PD-L1 testing is required before treatment with some drugs and recommended before others. Whether testing is required or recommended depends on the specific cancer and the type of drug. Your health care provider can discuss the current guidance for PD-L1 testing based on your specific situation.
Testing and treatments continue to evolve. Currently, PD-L1 testing may be used to help guide therapy for cancers such as:
- Non-small cell lung cancer
- Bladder cancer and related urothelial cancers
- Gastric or gastroesophageal junction adenocarcinoma, or esophageal squamous cell carcinoma
- Head and neck squamous cell carcinoma
- Cervical cancer
- Breast cancer
When is it ordered?
PD-L1 testing is ordered when you have been diagnosed with cancer and your healthcare practitioner wants to determine whether you would likely be a good candidate for treatment with a PD-L1 or PD-1 inhibitor.
Testing for PD-L1 may be required prior to treatment.
- Companion diagnostic: For some combinations of cancer and immunotherapies, testing is required before starting therapy.
- Complementary diagnostic: For some combinations, testing is recommended and expected but not required.
Sometimes PD-L1 testing is ordered when your cancer starts to grow again after chemotherapy or another drug treatment. It may be ordered when you have advanced cancer and limited treatment options, and PD-L1 immunotherapy is being considered.
What does the test result mean?
The results of PD-L1 testing may report that PD-L1 is present or absent (expressed or not expressed) in tumor tissue, or it may be reported as a score specific for the test that you had done. The report may also include an interpretation.
If PD-L1 protein is present on the tumor tissue, then you may be a good candidate for the immunotherapy drug being considered. Not every person who has a cancer with increased PD-L1 will respond to the immunotherapy, however, and your response may change over time.
If there is little or insufficient PD-L1 present, then it is less likely that you would benefit from the immunotherapy, and a different treatment is likely to be considered.
A negative result means that insufficient PD-L1 was present in the sample tested. The amount of PD-L1 can sometimes vary in different parts of the tumor. A biopsy sample may or may not be representative of most of the tumor. PD-L1 amounts can also vary over time, for example, being present in different quantities in the original tumor compared to a recurrent tumor.
How long does it take for PD-L1 testing results?
PD-L1 testing is not available in every laboratory. Depending on the test method used and whether or not a health care practitioner sends a sample to a reference laboratory, the results may take several days before they are available.
Can I have my blood tested instead of having a tissue biopsy?
For diagnosis of your tumor, you will need a tissue biopsy. Tissue cells from this biopsy are also required for PD-L1 testing.
Is testing before treatment really necessary?
Testing is required for cancers and drug combinations identified by the Food and Drug Administration (FDA) as needing “companion diagnostic testing.” Testing is common and considered the best practice when the combination is identified as “complementary diagnostic testing.” Use of immunotherapy drugs continues to evolve. As things change and more data become available, practices will also continue to change. Consult with your health care practitioner.
What are some side effects of immunotherapy?
Since PD-L1 can also be found on the surface of normal cells throughout the body, the use of immunotherapies can cause side effects related to these normal cells also being attacked by the immune system. Some common side effects include tiredness (fatigue), loss of appetite, nausea, coughing, skin rash and itching. Always discuss treatment decisions with your oncologist and carefully weigh the risks and benefits of each treatment. For more details, read the American Cancer Society’s article on Immune checkpoint inhibitors to treat cancer.
Is this test recommended for everyone with cancer?
No. PD-L1 testing is only required or recommended for people who have certain types of cancers if they are being considered for treatment with PD-L1 or PD-1 inhibitors. This test is not used to screen for or diagnose cancer. If you are diagnosed with cancer, talk to your cancer specialist about what treatment options may be available for you.
(2019 May 31, Updated). Non-Small Cell Lung Cancer Treatment (PDQ ®) – Patient Version. National Cancer Institute. Available online at https://www.cancer.gov/types/lung/patient/non-small-cell-lung-treatment-pdq#_164. Accessed on 9/14/19.
Dacic, S. (2018). Time is up for PD-L1 Testing Standardization in Lung Cancer. Medscape from Ann Oncol. 2018;29(4):791-792. Available online at https://www.medscape.com/viewarticle/897006. Accessed on 9/14/19.
Tan, W. and Huq, S. (2019 August 23, Updated). Non-Small Cell Lung Cancer (NSCLC). Medscape Oncology. Available online at https://emedicine.medscape.com/article/279960-overview. Accessed on 9/14/19.
(2019 April 15, Updated). PDL1 (Immunotherapy) Tests. MedlinePlus Medical Encyclopedia. Available online at https://medlineplus.gov/lab-tests/pdl1-immunotherapy-tests/. Accessed on 9/14/19.
LoCicero, R. et. al. (2018 January 16, Updated). Lung cancer – non-small cell. MedlinePlus Medical Encyclopedia. Available online at https://medlineplus.gov/ency/article/007194.htm Accessed on 9/14/19.
Deftereos, G. (2019 July, Updated). PD-L1 Testing. ARUP Consult. Available online at https://arupconsult.com/content/pd-l1-testing. Accessed on 9/14/19.
Harrison, P. (2019 September 12). Unprecedented Survival in Lung Cancer With Immunotherapy. Medscape Conference News WCLC 2019. Available online at https://www.medscape.com/viewarticle/918298. Accessed on 9/14/19.
Hernandez, A. et. al. (2019). Assessment of Programmed Death–ligand 1 (PD-L1) Immunohistochemical Expression on Cytology Specimens in Non–Small Cell Lung Carcinoma. Medscape from Am J Clin Pathol. 2019;151(4):403-415. Available online at https://www.medscape.com/viewarticle/909910. Accessed on 9/14/19.
Boggs, W. (2019 July 8). High Prevalence of PD-L1 Expression in Non-Small-Cell Lung Cancer. Medscape News Reuters Health Information. Available online at https://www.medscape.com/viewarticle/915266. Accessed on 9/14/19.
(2018 October 1, Updated). About Non-Small Cell Lung Cancer. American Cancer Society. Available online at https://www.cancer.org/content/dam/CRC/PDF/Public/8703.00.pdf. Accessed on 9/14/19.
(2019 April 18, Updated). Treating Non-Small Cell Lung Cancer. American Cancer Society. Available online at https://www.cancer.org/content/dam/CRC/PDF/Public/8706.00.pdf. Accessed on 9/14/19.
Jin, J. et. al. (2019 April 16). Identification of Genetic Mutations in Cancer: Challenge and Opportunity in the New Era of Targeted Therapy. Front Oncol. 2019; 9: 263. Available online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6477148/. Accessed on 9/14/19.
(2019 May). PD-L1 by Immunohistochemistry: Options for Companion and Complementary Diagnostic Assays. Mayo Clinic Laboratories. Available online at https://www.mayocliniclabs.com/it-mmfiles/PD-L1_Immunohistochemistry_Options.pdf. Accessed on 9/14/19.
(2018 October 1, Updated). Immune checkpoint inhibitors to treat cancer. American Cancer Society. Available online at https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/immune-checkpoint-inhibitors.html. Accessed on 9/14/19.
Pons-Tostivint, E. et. al. (2019). Comparative Analysis of Durable Responses on Immune Checkpoint Inhibitors Versus Other Systemic Therapies. Medscape from JCO Precis Oncol. 2019;2019(3). Available online at https://www.medscape.com/viewarticle/910044. Accessed on 9/14/19.
Douglas, D. (2019 May 3). Adverse Events Common With PD-1 and PD-L1 Inhibitors. Medscape News Reuter Health Information. Available online at https://www.medscape.com/viewarticle/912454. Accessed on 9/14/19.
Mulcahy, N. (2019 April 11). More Biomarkers Needed in Cancer Immunotherapy. Medscape Conference News NCCN 2019. Available online at https://www.medscape.com/viewarticle/911719. Accessed on 9/14/19.
Liu, J. et. al. (2018 December). Efficacy and safety of PD1/PDL1 blockades versus docetaxel in patients with pretreated advanced non-small-cell lung cancer: a meta-analysis. Onco Targets Ther. 2018 Dec 3;11:8623-8632. Available online at https://www.ncbi.nlm.nih.gov/pubmed/30584321. Accessed on 9/14/19.
Havel, J. et. al. (2019 March). The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy. Nat Rev Cancer. 2019 Mar;19(3):133-150. Available online at https://www.ncbi.nlm.nih.gov/pubmed/30755690. Accessed on 9/14/19.
(© 1995–2019). Programmed Death-Ligand 1 (PD-L1) (SP263), Semi-Quantitative Immunohistochemistry, Manual. Mayo Clinic Laboratories. Available online at https://www.mayocliniclabs.com/test-catalog/Clinical+and+Interpretive/603755. Accessed on 9/14/19.
(© 1995–2019). Programmed Death-Ligand 1 (PD-L1) (SP142), Semi-Quantitative Immunohistochemistry, Manual. Mayo Clinic Laboratories. Available online at https://www.mayocliniclabs.com/test-catalog/Overview/603769. Accessed on 9/14/19.
(© 1995–2019). Programmed Death-Ligand 1 (PD-L1) (22C3), Semi-Quantitative Immunohistochemistry, Manual. Mayo Clinic Laboratories. Available online at https://www.mayocliniclabs.com/test-catalog/Overview/603762. Accessed on 9/14/19.
(© 2019). Immune Checkpoint Inhibitors. MD Anderson Cancer Center. Available online at https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/immune-checkpoint-inhibitors.html. Accessed on 9/14/19.