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Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitor Therapy
Adrienne K Ho1, Anthony M-H Ho2, Tim Cooksley3
1From the Department of Clinical Oncology, Manchester University NHS Foundation Trust, Manchester, United Kingdom.
Abstract:
As part of immune surveillance, killer T lymphocytes search for cancer cells and destroy them. Some cancer cells, however, develop escape mechanisms to evade detection and destruction. One of these mechanisms is the expression of cell surface proteins which allow the cancer cell to bind to proteins on T cells called checkpoints to switch off and effectively evade T-cell-mediated destruction. Immune checkpoint inhibitors (ICIs) are antibodies that block the binding of cancer cell proteins to T-cell checkpoints, preventing the T-cell response from being turned off by cancer cells and enabling killer T cells to attack. In other words, ICIs restore innate antitumor immunity, as opposed to traditional chemotherapies that directly kill cancer cells. Given their relatively excellent risk-benefit ratio when compared to other forms of cancer treatment modalities, ICIs are now becoming ubiquitous and have revolutionized the treatment of many types of cancer. Indeed, the prognosis of some patients is so much improved that the threshold for admission for intensive care should be adjusted accordingly. Nevertheless, by modulating immune checkpoint activity, ICIs can disrupt the intricate homeostasis between inhibition and stimulation of immune response, leading to decreased immune self-tolerance and, ultimately, autoimmune complications. These immune-related adverse events (IRAEs) may virtually affect all body systems. Multiple IRAEs are common and may range from mild to life-threatening. Management requires a multidisciplinary approach and consists mainly of immunosuppression, cessation or postponement of ICI treatment, and supportive therapy, which may require surgical intervention and/or intensive care. We herein review the current literature surrounding IRAEs of interest to anesthesiologists and intensivists. With proper care, fatality (0.3%-1.3%) is rare.
Insights
Immune checkpoint inhibitors (ICIs) unleash T cells to fight cancer but can cause autoimmune complications. Management involves immunosuppression and supportive care, with rare fatalities.
Area of Science:
- Oncology
- Immunology
- Anesthesiology
- Intensive Care Medicine
Background:
- Killer T lymphocytes are crucial for immune surveillance against cancer.
- Cancer cells evade T cell destruction via immune checkpoint proteins.
- Immune checkpoint inhibitors (ICIs) block these checkpoints, restoring antitumor immunity.
Purpose of the Study:
- To review immune-related adverse events (IRAEs) associated with ICIs.
- To highlight IRAEs relevant to anesthesiologists and intensivists.
- To discuss management strategies for ICI-induced complications.
Main Methods:
- Literature review of current research on ICI-related IRAEs.
- Focus on IRAEs affecting various body systems.
- Analysis of management approaches including immunosuppression and supportive care.
Main Results:
- ICIs revolutionize cancer treatment but can cause autoimmune complications by disrupting immune homeostasis.
- IRAEs affect all body systems, can be multiple, and range from mild to life-threatening.
- Fatality rates from IRAEs are low (0.3%-1.3%) with appropriate multidisciplinary management.
Conclusions:
- ICIs offer significant benefits in cancer therapy but necessitate vigilance for IRAEs.
- Multidisciplinary management, including immunosuppression and supportive care, is crucial for IRAEs.
- Anesthesiologists and intensivists play a key role in managing patients experiencing severe IRAEs.
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