Checkpoint inhibitors

The body consists mainly of two types of immune cells. Innate immune cells are the first line of defense, targeting invaders at the first sign of an infection or inflammation. Adaptive immune cells, like T-cells, are more selective, attacking specific antigens.

T-cells roam the body looking for foreign cells by using proteins called receptors on their surfaces to exchange signals with other cells. During this exchange of signals, called a checkpoint, if a T-cell determines a cell is normal or healthy, it moves on to check other cells. Because cancer cells are the body's own mutated cells, the immune system does not always recognize them as foreign. And cancer cells may send deceptive signals at checkpoints that tell T-cells they are not harmful.

Checkpoint inhibitors work by blocking the receptors that cancer cells use to send signals to T-cells. When the signal is blocked, T-cells may be better able to differentiate a cancer cell from a healthy cell and launch an attack.

Before prescribing a checkpoint inhibitor to treat cancer, a doctor may look for certain genetic features, called biomarkers, on cancers cells that may indicate the drug will produce a positive outcome. Those biomarkers include:

• PD-L1 is a protein often found on some cancer cells. When the PD-L1 protein on a cancer cell interacts with the PD-1 protein on an immune cell, the cancer cell is considered healthy and is left alone. Some checkpoint inhibitors are designed to block either PD-1 or PD-L1, exposing the cancer cell for attack.
• CTLA-4 is another type of protein found on certain T-cells that can give cancer a free pass to spread. However, blocking it can help T-cells recognize and attack cancer cells.
• Microsatellite instability (MSI-H) or mismatch repair (dMMR) are mutations in cells that make it difficult for the DNA in a cell to repair itself, which may lead to unchecked cell growth. The decision to approve checkpoint inhibitors to treat cancers with MSI-H or dMMR marked the first time in history a drug was approved for cancer treatment based on a genetic feature.

A patient’s cancer does not need to test positive for these biomarkers to receive this immunotherapy treatment. Checkpoint inhibitors are often prescribed for advanced cancers, such as melanoma, kidney and bladder cancers. It may also be a first-line treatment for some cases of lung cancer.

Because checkpoint inhibitors stimulate the immune system, they may cause immune cells to attack healthy cells, triggering a variety of side effects, including fatigue, nausea and diarrhea and flu-like symptoms.

A rarer side effect of checkpoint inhibitors includes inflammation. This can lead to a host of issues depending on which organs are affected, including:

• Skin changes, such as rash and itchiness
• Cough, chest pain and difficulty breathing
• Abdominal pain and diarrhea
• Diabetes
• Hepatitis (liver inflammation)
• Hypophysitis (pituitary gland inflammation)
• Myocarditis (heart muscle inflammation)
• Nephritis (kidney inflammation) and impaired kidney function
• Overactive or underactive thyroid gland
• Muscle weakness and numbness

Throughout your treatment, your care team may offer supportive care services to help reduce side effects.