Autoimmunity, checkpoint inhibitor therapy and immune-related adverse events: A review
Immune checkpoint inhibitors have emerged as a remarkable treatment option for diverse cancer types. However, a significant number of patients on checkpoint inhibitors develop immune-related adverse events (irAEs) affecting a wide variety of organs. These events, which may reflect enhanced T cell ac...
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| Published in | Seminars in cancer biology Vol. 64; pp. 93 - 101 |
|---|---|
| Main Authors | , |
| Format | Journal Article |
| Language | English |
| Published |
England
Elsevier Ltd
01.08.2020
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Immune checkpoint inhibitors have emerged as a remarkable treatment option for diverse cancer types. However, a significant number of patients on checkpoint inhibitors develop immune-related adverse events (irAEs) affecting a wide variety of organs. These events, which may reflect enhanced T cell activation, are unpredictable, heterogeneous, and in some instances permanent or life-threatening. It is not clear whether these toxicities are distinct from conventional autoimmune diseases or whether the manifestation of irAEs is associated with therapeutic efficacy. Studies across the spectrum of basic, preclinical and clinical research deciphering the role of genetics, epigenetics, gut microbiota and underlying immune status of patients who develop irAEs are required to gain a deeper mechanistic understanding. Insights gained from such studies will facilitate identification of biomarkers for optimal treatment and clinical management of patients. In this Review, we provide basic and clinical understanding of immune checkpoint inhibitors and irAEs. We discuss the connection between immune system, autoimmunity and cancer; immune checkpoint inhibitors and associated autoimmune toxicities; insights into potential underlying mechanisms of irAEs; impact of autoimmune diagnosis on cancer outcome; and management of irAEs. |
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| AbstractList | Immune checkpoint inhibitors have emerged as a remarkable treatment option for diverse cancer types. However, a significant number of patients on checkpoint inhibitors develop immune-related adverse events (irAEs) affecting a wide variety of organs. These events, which may reflect enhanced T cell activation, are unpredictable, heterogeneous, and in some instances permanent or life-threatening. It is not clear whether these toxicities are distinct from conventional autoimmune diseases or whether the manifestation of irAEs is associated with therapeutic efficacy. Studies across the spectrum of basic, preclinical and clinical research deciphering the role of genetics, epigenetics, gut microbiota and underlying immune status of patients who develop irAEs are required to gain a deeper mechanistic understanding. Insights gained from such studies will facilitate identification of biomarkers for optimal treatment and clinical management of patients. In this Review, we provide basic and clinical understanding of immune checkpoint inhibitors and irAEs. We discuss the connection between immune system, autoimmunity and cancer; immune checkpoint inhibitors and associated autoimmune toxicities; insights into potential underlying mechanisms of irAEs; impact of autoimmune diagnosis on cancer outcome; and management of irAEs. |
| Author | Khan, Shaheen Gerber, David E. |
| AuthorAffiliation | 2 Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390-9093 3 Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390-9093 1 Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, 75390-9093 4 Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, 75390-9093 |
| AuthorAffiliation_xml | – name: 2 Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390-9093 – name: 4 Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, 75390-9093 – name: 1 Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, 75390-9093 – name: 3 Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390-9093 |
| Author_xml | – sequence: 1 givenname: Shaheen surname: Khan fullname: Khan, Shaheen email: Shaheen.khan@utsouthwestern.edu organization: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, 75390-9093, United States – sequence: 2 givenname: David E. surname: Gerber fullname: Gerber, David E. email: David.Gerber@utsouthwestern.edu organization: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390-9093, United States |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31330185$$D View this record in MEDLINE/PubMed |
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| Keywords | Autoimmunity Immune checkpoint inhibitors Immunotherapy Toxicity and irAEs |
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| SubjectTerms | Animals Autoimmune Diseases - etiology Autoimmune Diseases - pathology Autoimmunity Autoimmunity - immunology Biomarkers, Tumor - antagonists & inhibitors Biomarkers, Tumor - immunology Humans Immune checkpoint inhibitors Immunologic Factors - adverse effects Immunotherapy Immunotherapy - adverse effects Neoplasms - immunology Neoplasms - pathology Neoplasms - therapy Toxicity and irAEs |
| Title | Autoimmunity, checkpoint inhibitor therapy and immune-related adverse events: A review |
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