Different medical terms are used in defining other medical terms. When advertisements on the television for new immunotherapy drugs say that in order for the new drug to be effective the tumor must “express PD-L1”, what are they talking about? Although the words are long and foreign the new classification of therapy and its results are exciting for all patients and families.
To review, the immune system as defined on www.cancer.gov:
“A complex network of cells, tissues, organs, and the substances they make that helps the body fight infections and other diseases. The immune system includes white blood cells and organs and tissues of the lymph system, such as the thymus, spleen, tonsils, lymph nodes, lymph vessels, and bone marrow.”
It is long known that the immune system plays a vital role in keeping us healthy. The way the immune system functions are to recognize and fight foreign invaders that will change the cell metabolism.
It was discovered over 100 years ago that somehow the immune cells allowed other infiltrates to produce cells that are undetected and cause disease. Why or how this happened was a mystery. What controlled the switch to allow this to happen? In the 1990’s the breakthrough discovery by scientists that human cells carry certain proteins on their surface that enable them to escape attack from the body’s immune system. This led to the discovery in 2000 by scientists at Dana Farber Cancer Institute in Boston. The scientist credited with its discovery is Gordon Freeman PhD and his associates. What Dr. Freeman discovered is that the protein PD-L1 (programmed cell death 1 ligand 1) was on normal cells. Their research discovered that PD-L1 binds to the T cells co-receptor PD-1 as a result the T cell does not start the immune system from attacking. In 2001 Dr. Freeman and his associates published that PD-L1 appears not only on some normal cells but on certain cancer cells as well. From that it was thought that the agent that blocks PD-L1(or a related ligand PD-L2) could release the brakes on the immune system and attack the cancer. From these discoveries, pharmaceutical companies started to look at drugs that could block PD-1, PD-L1, or PD-L2. The drugs that block these and other proteins are known as immune checkpoint inhibitors.
The definition for immune checkpoint inhibitor, according to www.cancer.gov:
“A type of drug that blocks certain proteins made by some types of immune cells, such as T cells, and some cancer cells. These proteins help keep immune responses in check and can keep T cells from killing cancer cells. When these proteins are blocked, the “brakes” on the immune system are released and T cells can kill cancer cells better. Examples of checkpoint proteins found on T cells or cancer cells include PD-1/PD-L1 and CTLA-4/B7-1/B7-2. Some immune checkpoint inhibitors are used to treat cancer.”
Our immune system is comprised of many cells including T cells. T cells help fight off diseases like cancer. On the surface of the T cells are certain proteins known as programmed cell death receptors, or called PD-1. The cancer cells can escape T cells by expressing a protein called PD-L1. This protein activates t cells. PD-L1 attach to T cell receptors called PD-1. The scientists have theorized if we could prevent the cancer cells from expressing PD-L1 we could treat the cancers that express this gene.
The goal of cancer immunotherapy is to increase the immune systems response to cancer. Targeting PD-L1 is very important in cancer research. Cancer immunogenicity is the ability of a tumor to start an immune response. The more mutations a tumor has, the higher the chance that tumor antigens can trigger the immune response.
The drugs that are targeted as PD-1 inhibitors are Pembrolizumab (keytruda) or Nivolumab (Opdivo). Currently these drugs have had positive effects on certain types of cancers: Melanoma of the skin, non-small cell lung cancer, kidney cancer, bladder cancer, head and neck cancers, and Hodgkin lymphoma.
PD-L1 inhibitors include Atezolizumab (Tecentriq) and Avelumab (Bavencio). These drugs have been used to treat bladder cancer, non-small cell lung cancer, and Merkel cell skin cancer (Merkel cell carcinoma).
For patients with malignant mesothelioma there are currently clinical trials available with immunotherapy. In the Mesothelioma Clinical Trial Digest, you can find listings of the sites and the drugs they are trialing.
So, the next time that you hear the cancer must express PD-L1 to be eligible for a certain medication, this is what PD-L1 is.