PD-L1 and PD-1

This page was reviewed under our medical and editorial policy by

Sagun Shrestha, MD, Medical Oncologist and Hematologist

This page was updated on March 16, 2023.

Immunotherapy is a biological therapy that uses matter made from living organisms as a treatment for cancer. This type of cancer treatment is designed to improve the immune system’s ability to identify and destroy cancer cells. Immunotherapy is used for a wide range of cancers and may be used as either a standalone treatment or combined with chemotherapy or other treatments.

One type of immunotherapy uses drugs called immune checkpoint inhibitors. A standard part of the immune system, immune checkpoints are almost like security stations in cells. They occur naturally in the body and prevent the immune system from working so strongly that it accidentally harms healthy cells.

The “checkpoint” is an interaction between cells and immune T-cells. T-cells move around the body searching for foreign cells via proteins on their surfaces (called receptors). In this exchange (or checkpoint), a T-cell may detect whether a cell is a threat, and if not, the immune system is turned off and the T-cells search elsewhere.

However, as mutated cells, tumor cells sometimes appear as healthy cells to the immune system by relaying misleading signals to the T-cells. Tumor cells sometimes have proteins that tell the immune system to turn off and stop destroying cancer cells.

Immune checkpoint inhibitor medication blocks this potential miscommunication from happening, allowing the body’s T-cells to destroy tumors.

However, not all types of immunotherapies work for all patients. To determine whether immunotherapy may be appropriate, doctors may use biomarker testing to determine whether the cancer type may respond well to immunotherapy. Biomarker testing looks for certain proteins or genes in a tumor (known as biomarkers). Biomarkers are important because they reveal significant information about the cancer, as every patient has his or her own distinct patterns of biomarkers, so biomarker testing may help identify whether certain treatments will be appropriate for a specific patient’s cancer.

PD-L1 and PD-1 are two types of immune checkpoints that may be targeted with checkpoint inhibitors to help treat certain types of cancer. Here’s what patients need to know about PD-L1 and PD-1 checkpoint inhibitors.

What are PD-L1 and PD-1?

PD-L1 (programmed cell death ligand 1) is a protein in certain healthy cells. While PD-L1 is found in normal cells, it’s also found on some types of cancer cells, and in higher-than-normal levels. PD-1 (programmed cell death protein 1) is a type of protein found in the body’s T-cells that helps regulate the immune system.

When the two proteins bind together, this creates an immune checkpoint and tells the T-cells to stop destroying cells that contain PD-L1, which may include certain cancer cells. This allows cancer cell numbers to increase and go undetected by the immune system.

Immune checkpoint inhibitor drugs may stop the two proteins from binding together, which allows the T-cells to destroy cancer cells.

PD-1 and PD-L1 in immunotherapy

By treating patients with checkpoint inhibitor drugs, it may be possible to slow down the growth of certain types of cancers by altering either PD-1 or PD-L1 levels in the body.

Breast cancer

Research shows that increased PD-L1 levels are associated with breast cancer growth, so PD-L1-limiting drugs may be used as a treatment option. These may include drugs such as Tecentriq® (atezolizumab).

Lung cancer

In lung cancer patients, increased PD-L1 levels are linked to advanced cancer. Checkpoint inhibitor drugs for lung cancer may include Keytruda® (pembrolizumab).

Prostate cancer

Increased PD-L1 levels have been linked with poor outcomes in prostate cancer patients.

Pancreatic cancer

For patients with pancreatic cancer, reducing levels of PD-L1 in the body may be used as a treatment option. Studies show that blocking PD-L1 may suppress pancreatic cancer cells. A PD-L1 inhibitor drug may be used for pancreatic cancer patients, such as Jemperli (dostarlimab-gxly) or pembrolizumab.

Diffuse large B-cell lymphoma (DLBCL)

High levels of PD-L1 are linked to DLBCL tumors, so PD-L1 inhibitors such as pembrolizumab may be used as a treatment option.

Bladder cancer

In bladder cancer patients, higher levels of PD-L1 have been linked to advanced cancer types and lower survival rates. A PD-L1 inhibitor drug such as Bavencio® (avelumab) or Opdivo® (nivolumab) may be administered for bladder cancer patients.

PD-L1 testing

In addition to the above types of cancer, other cancers may benefit from PD-L1 testing, including:

The testing measures the amount of PD-L1 in cancer cells, which may help doctors determine whether immunotherapy may be helpful. PD-L1 testing is generally performed via a biopsy, where cell samples are removed either surgically or with a needle. Depending on the type of biopsy, local or general anesthesia is given so the patient won’t be uncomfortable.

The types of biopsies used for PD-L1 testing include those below.

  • Fine needle aspiration: A very thin needle is used to remove fluid or cells from the body.
  • Core needle biopsy: A sample of cells or fluid is removed using a larger-sized needle.
  • Surgical biopsy: A sample of cells or fluid are removed via an outpatient surgical procedure, using an incision to remove all or part of the tumor.

Understanding test results

When test results are ready, the doctor meets with the patient to discuss the results. A PD-L1 test may show high levels of PD-L1 in the tumor, meaning it’s PD-L1 positive, indicating that the patient may be a candidate for immunotherapy.

If the test is negative, meaning the tumor has low PD-L1 levels, immunotherapy may not be used. In that case, a doctor may recommend additional tests or suggest other treatment options.

It’s normal to feel worried or confused when receiving test results, so patients should ask their doctor if they have any questions about what their results mean for their treatment plan.

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