PD-1

PD-1 is a protein found on immune cells called T cells. The PD-1 protein helps regulate the body’s immune response: when PD-1 attaches to another protein called a ligand, PD-L1, they block the T cells from attacking other cells, including both healthy and cancer cells. PD-1 inhibition is the mechanism of some anticancer drugs, which allow the T cells to have their normal function and attack cancer cells. PD-1 inhibitors fall into a class of immunotherapy drugs known as checkpoint inhibitors. (Checkpoints are the proteins that keep the immune system from targeting normal cells.) Currently there are two PD-1 inhibitors approved by the US Food and Drug Administration available for immunotherapy treatment: Nivolumab and pembrolizumab. Clinical indications for these drugs include:

  • Lung cancer
  • Bladder cancer
  • Melanoma
  • Head and neck cancers
  • Kidney cancer
  • Hodgkin lymphoma

Because these drugs activate the immune system, it is possible some healthy tissues are affected by the activated immune system during treatment and lead to some unique potential treatment-related adverse events, sometimes referred to as irTEAEs (immune-related, treatment-emergent adverse events). This can lead to problems in the lungs, intestines, liver, kidneys, hormone-making glands, and other organs may occur. These irTEAEs are quite different from the typical side effects of chemotherapy and have been well-characterized. They include:

  • Fatigue (due to hypophysitis)
  • Cough or shortness of breath (due to pneumonitis)
  • Nausea, abdominal pain, diarrhea (due to colitis)
  • Joint pain (arthritis)
  • Skin rash (dermatitis)

The patient response to PD-1 inhibition immunotherapy varies and can be long lasting or demonstrate short-lived tumor shrinkage, and sometimes no response is reported at all. Studies indicate that the mechanism of PD-1 inhibition is most effective when treating tumors that developed as a result of genetic mutations (often associated with smoking) and that demonstrate high levels of DNA damage.