To start an immune system response to a foreign invader, the immune system has to be able to tell the difference between cells or substances that are “self” (part of you) versus “non-self” (not part of you and possibly harmful). Your body’s cells have proteins on their surfaces or inside them that help the immune system recognize them as “self.”
Some of these proteins that help your immune system recognize “self” cells are called immune checkpoints. Cancer cells sometimes find ways to use these immune checkpoint proteins as a shield to avoid being identified and attacked by the immune system.
Immune system cells called T cells roam throughout the body looking for signs of disease or infection. When T cells meet another cell, they analyze certain proteins on the cell’s surface, which helps the T cell identify the cell. If the surface proteins signal that the cell is normal and healthy, the T cell leaves it alone. If the surface proteins suggest the cell is cancerous or unhealthy in another way, the T cell starts an attack against it. Once T cells start an attack, the immune system begins to make more specialized proteins that prevent this attack from damaging normal cells and tissues in the body. These specialized proteins that keep healthy cells and tissues safe are called immune checkpoints.
Immune checkpoint inhibitors target these immune checkpoint proteins and help the immune system recognize and attack cancer cells. Immune checkpoint inhibitors essentially take the brakes off the immune system by blocking checkpoint inhibitor proteins on cancer cells or on the T cells that respond to them.
For example, PD-1 is a checkpoint protein on T cells. PD-L1 is another checkpoint protein found on many healthy cells in the body. When PD-1 binds to PD-L1, it stops T cells from killing a cell.
Still, some cancer cells have a lot of PD-L1 on their surface, which stops T cells from killing these cancer cells. An immune checkpoint inhibitor medicine that stops PD-1 from binding to PD-L1 allows T cells to attack the cancer cells.
Some PD-1 and PD-L1 inhibitors that have been approved by the U.S. Food and Drug Administration (FDA) to treat cancers other than breast cancer are:
- Keytruda (chemical name: pembrolizumab), used to treat advanced-stage skin cancer, certain types of non-small cell lung cancer, advanced-stage head and neck squamous cell cancer, Hodgkin lymphoma, advanced-stage urothelial cancer, and advanced-stage cancers with microsatellite instability-high or mismatch repair deficient, a specific type of genetic marker
- Opdivo (chemical name: nivolumab), used to treat metastatic non-small cell lung cancer, Hodgkin lymphoma, advanced-stage renal cell cancer, advanced-stage urothelial cancer, advanced-stage head and neck squamous cell cancer, and metastatic skin cancer
- Tecentriq (chemical name: atezolizumab), used to treat advanced-stage urothelial cancer and metastatic non-small cell lung cancer
- Bavencio (chemical name: avelumab), used to treat a rare type of metastatic skin cancer called Merkel cell carcinoma and advanced-stage urothelial cancer
- Imfinzi (chemical name: durvalumab), used to treat advanced-stage urothelial cancer
Clinical trials are studying all these and other PD-1/PD-L1 inhibitors to treat breast cancer.
CTLA-4 is another checkpoint protein on some T cells. When CTLA-4 binds to the B7 protein on another cell, it stops the T cell from killing the cell.
The CTLA-4 inhibitor medicine Yervoy (chemical name: ipilimumab) targets the CTLA-4 protein and stops it from binding to B7 on other immune cells. This pushes the T cells to become activated to attack cancer cells. Yervoy has been approved by the FDA to treat advanced-stage skin cancer. It is also being studied to treat breast and other cancers.
One big concern about immune checkpoint inhibitor medicines is that they may allow the immune system to attack some healthy cells and organs. Because the medicines essentially take the brakes off the immune system, T cells may start attacking cells other than cancer cells. Some serious side effects include problems with the lungs, liver, intestines, pancreas, and kidneys.
Right now, no immune checkpoint inhibitors have been approved by the U.S. Food and Drug Administration to treat breast cancer.