PD-L1, PD1, TMB and Lung Cancer

Understanding the Roles of PD-L, PD1 and TMB in Lung Cancer Treatment

The videos above were produced in 2020. For the latest treatment options, speak with your doctor.

Support for this educational program provided by Amgen, AstraZeneca, Blueprint Medicines, Bristol Myers Squibb, Genentech, Lilly Oncology, Merck, Novartis and Pfizer.

Researchers have identified certain biomarkers in lung cancer tumors. PD-L1 and TMB are biomarkers that may help provide information about whether or not a patient will benefit from immunotherapy to treat their lung cancer. Immunotherapy doesn’t kill cancer directly like chemotherapy. Instead, it helps your immune system recognize and attack cancer cells that were previously “hiding.” Immunotherapy activates the immune system to attack these cancer cells. The most common type of lung cancer immunotherapy is called an immune checkpoint inhibitor. Several immune checkpoint inhibitors for lung cancer block, or “inhibit” the interaction between PD-1 and PD-L1.

What are PD-L1 and PD-1?

PD-1 is a receptor often on the surface of immune cells, such as T-cells — the very cells responsible for recognizing and attacking abnormal cells, including cancer. Under normal conditions, PD-1 helps prevent excessive or mistaken attacks by acting as a “brake” on T-cells. Tumors can exploit that mechanism by producing PD-L1 (or related ligands), which bind to PD-1 and switch off T-cell activity. Immune checkpoint inhibitors block this interaction to release the “brake” and allow T-cells to detect and kill cancer cells. While many lung cancer patients are tested for PD-L1 levels in their tumors, the presence (and function) of PD-1 on immune cells is equally important for the success of immunotherapy.

PD-L1 is a protein that has a broader presence, including on the tumor cells. High-levels of PD-L1 is one biomarker that doctors look for in patients with lung cancer. Some immune checkpoint inhibitors can also target another type of immune protein called CTLA-4 and are used with PD-L1 inhibitors.

How do you know your levels of PD-L1 and what do they mean?

At the time of a lung cancer diagnosis, all new patients should have their PD-L1 levels tested. This involves looking at tumor tissue under a microscope using a laboratory technique called immunohistochemical (IHC) staining. A PD-L1 test is reported as a percentage, measuring how much cells in a tumor “express” PD-L1. Tumors that express high amounts of PD-L1 (50% or greater) may respond particularly well to immune checkpoint inhibitors.

If you have not had your PD-L1 levels tested, ask your doctor if it is right for you.

Learn more about the different types of biomarker tests.

How does PD-L1 level impact treatment options?

Results of PD-L1 tests help to inform treatment options. If you have high levels of PD-L1 and no other biomarker with an approved targeted therapy, then your doctor will likely recommend an immunotherapy drug as a first-line treatment. This means you get an immunotherapy drug before any other treatment. You may also receive chemotherapy at the same time.

If you have some expression of PD-L1, but less than 50%, your doctor may recommend a combination of immunotherapy and chemotherapy. Ask your doctor about your PD-L1 levels, any other biomarkers, and what they mean for your treatment options.

What is TMB?

TMB stands for tumor mutation burden. Tumor mutation burden measures the number of genetic mutations found in a tumor's DNA. These changes can cause cancer cells to make abnormal proteins. For immunotherapy to work, the immune system must recognize one or more of these abnormal proteins. That is why tumors with a higher TMB, meaning more genetic mutations, may have a better chance of responding well to immunotherapy. Talk with your doctor about this test and if it is right for you.

Work with your doctor to discuss your goals and options each time you have to make a treatment decision. The three big questions to ask are:

1. What is the goal of this treatment?
2. What are the potential side effects?
3. What other options do I have?

Research is happening at a rapid pace, and your doctor should be up to date on the recommendations for your specific type of lung cancer. If you don’t feel comfortable with the answers you are receiving, do not hesitate to seek out a second opinion.