Immune Checkpoint Inhibitors and Their Side Effects

An important function of the immune system is its ability to tell between normal cells in the body and those it sees as “foreign.” This lets the immune system attack the foreign cells while leaving the normal cells alone. To do this, it uses “checkpoints.” Immune checkpoints are molecules on certain immune cells that need to be activated (or inactivated) to start an immune response.

Cancer cells sometimes find ways to use these checkpoints to avoid being attacked by the immune system. But drugs that target these checkpoints hold a lot of promise as cancer treatments. These drugs are called checkpoint inhibitors.

It's important to know that checkpoint inhibitors used to treat cancer don't work directly on the tumor at all. They only take the brakes off an immune response that has begun but hasn't yet been working at its full force.

Checkpoint inhibitor drugs that target PD-1 or PD-L1

PD-1 is a checkpoint protein on immune cells called T cells. It normally acts as a type of “off switch” that helps keep the T cells from attacking other cells in the body. It does this when it attaches to PD-L1, a protein on some normal (and cancer) cells. When PD-1 binds to PD-L1, it basically tells the T cell to leave the other cell alone. Some cancer cells have large amounts of PD-L1, which helps them hide from an immune attack.

Monoclonal antibodies that target either PD-1 or PD-L1 can block this binding and boost the immune response against cancer cells. These drugs have shown a great deal of promise in treating certain cancers.

PD-1 inhibitors: These drugs are given by IV (intravenously). Examples of drugs that target PD-1 include:

  • Pembrolizumab (Keytruda)
  • Nivolumab (Opdivo)
  • Cemiplimab (Libtayo)

These drugs have been shown to be helpful in treating several types of cancer, and new cancer types are being added as more studies show these drugs to be effective.

PD-L1 inhibitors: Examples of drugs that target PD-L1 include:

  • Atezolizumab (Tecentriq)
  • Avelumab (Bavencio)
  • Durvalumab (Imfinzi)

These drugs have also been shown to be helpful in treating different types of cancer, and are being studied for use against others.

Checkpoint inhibitor drugs that target CTLA-4

CTLA-4 is another protein on some T cells that acts as a type of “off switch” to keep the immune system in check.

Ipilimumab (Yervoy) is a monoclonal antibody that attaches to CTLA-4 and stops it from working. This can boost the body’s immune response against cancer cells.

This drug is used to treat melanoma of the skin and continues to be tested for other cancers.

Side effects of checkpoint inhibitors

The most common side effects of checkpoint inhibitors are:

  • Diarrhea
  • Pneumonitis (inflammation in the lungs)
  • Rashes and itchiness
  • Problems with some hormone levels
  • Kidney infections

If the side effects are severe, your doctor might delay giving the checkpoint inhibitor for a period of time to allow the body to recover. Less severe side effects can often be helped with medications.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

American Society of Clinical Oncology (ASCO). ASCO Annual Meeting 2019: Immunotherapy for lung cancer, gastrointestinal cancers and targeted therapy for breast cancer. Accessed at https://www.cancer.net/blog/2019-06/asco-annual-meeting-2019-immunotherapy-lung-cancer-gastrointestinal-cancers-and-targeted-therapy on December 19, 2019.

American Society of Clinical Oncology (ASCO). Understanding immunotherapy. Accessed at https://www.cancer.net/navigating-cancer-care/how-cancer-treated/immunotherapy-and-vaccines/understanding-immunotherapy on December 19, 2019.

Bayer VR, Davis ME, Gordan RA, et al. Immunotherapy. In Olsen MM, LeFebvre KB, Brassil KJ, eds. Chemotherapy and Immunotherapy Guidelines and Recommendations for Practice. Pittsburgh, PA: Oncology Nursing Society; 2019:149-189.

Kaunitz GJ, Loss M, Rizvi et al. Cutaneous eruptions in patients receiving immune checkpoint blockade: Clinicopathologic analysis of the nonlichenoid histologic pattern. Am J Surg Pathol. 2017; 41(10):1381-1389.

References

American Society of Clinical Oncology (ASCO). ASCO Annual Meeting 2019: Immunotherapy for lung cancer, gastrointestinal cancers and targeted therapy for breast cancer. Accessed at https://www.cancer.net/blog/2019-06/asco-annual-meeting-2019-immunotherapy-lung-cancer-gastrointestinal-cancers-and-targeted-therapy on December 19, 2019.

American Society of Clinical Oncology (ASCO). Understanding immunotherapy. Accessed at https://www.cancer.net/navigating-cancer-care/how-cancer-treated/immunotherapy-and-vaccines/understanding-immunotherapy on December 19, 2019.

Bayer VR, Davis ME, Gordan RA, et al. Immunotherapy. In Olsen MM, LeFebvre KB, Brassil KJ, eds. Chemotherapy and Immunotherapy Guidelines and Recommendations for Practice. Pittsburgh, PA: Oncology Nursing Society; 2019:149-189.

Kaunitz GJ, Loss M, Rizvi et al. Cutaneous eruptions in patients receiving immune checkpoint blockade: Clinicopathologic analysis of the nonlichenoid histologic pattern. Am J Surg Pathol. 2017; 41(10):1381-1389.

Last Medical Review: December 27, 2019 Last Revised: December 27, 2019

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