Adverse Events Following Cancer Immunotherapy: Obstacles and Opportunities

Oncology has recently undergone a revolutionary change with widespread adoption of immunotherapy for many cancers. Immunotherapy using monoclonal antibodies against checkpoint molecules, including programmed death (PD)-1, PD ligand (PD-L)1, and cytotoxic T lymphocyte-associated antigen (CTLA)-4, is...

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Vydáno v:Trends in immunology Ročník 40; číslo 6; s. 511 - 523
Hlavní autoři: Pauken, Kristen E., Dougan, Michael, Rose, Noel R., Lichtman, Andrew H., Sharpe, Arlene H.
Médium: Journal Article
Jazyk:angličtina
Vydáno: England Elsevier Ltd 01.06.2019
Elsevier Limited
Témata:
Adaptive immunity
Antigens
Autoimmune diseases
autoimmunity
Cancer immunotherapy
Cancer therapies
checkpoint blockade
Clinical trials
Cloning
Cytotoxicity
Disease
Etiology
Hepatitis
Immune checkpoint
Immune system
immune-related adverse events
Immunoglobulins
Immunotherapy
Inflammatory bowel disease
Inflammatory diseases
Lymphocytes
Lymphocytes T
Melanoma
Monoclonal antibodies
Oncology
tolerance
Viral infections
checkpoint blockade
autoimmunity
tolerance
cancer immunotherapy
immune-related adverse events
ISSN:1471-4906, 1471-4981, 1471-4981
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Shrnutí:Oncology has recently undergone a revolutionary change with widespread adoption of immunotherapy for many cancers. Immunotherapy using monoclonal antibodies against checkpoint molecules, including programmed death (PD)-1, PD ligand (PD-L)1, and cytotoxic T lymphocyte-associated antigen (CTLA)-4, is effective in a significant subset of patients. However, immune-related adverse events (irAEs) have emerged as frequent complications of checkpoint blockade, likely due to the physiological role of checkpoint pathways in regulating adaptive immunity and preventing autoimmunity. As immunotherapy becomes more common, a better understanding of the etiology of irAEs and ways to limit these events is needed. At the same time, studying these new therapy-related disorders provides an opportunity to better understand naturally occurring human autoimmune and inflammatory disorders, with the potential to improve therapies for cancer and autoimmune diseases. IrAEs represent a major obstacle for safely administering checkpoint blockade in cancer patients. Developing methods to minimize irAEs while maintaining effective antitumor immunity could make immunotherapy safer for more cancer patients. Diverse mechanisms likely drive irAEs, which may share varying degrees of similarities and differences with spontaneous autoimmunity. IrAEs that develop following checkpoint blockade in cancer provide an opportunity to better understand spontaneous autoimmune and inflammatory disorders. A deeper understanding of why some patients develop irAEs and others do not is needed to determine who is at highest risk for developing life threatening irAEs and to develop biomarkers to identify these individuals. Improvements in managing, investigating, and reporting on these irAEs are needed to reduce clinical challenges and maximize opportunities to learn from irAEs.
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ISSN:1471-4906
1471-4981
1471-4981
DOI:10.1016/j.it.2019.04.002