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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Bibliographic Details
Published inSeminars in cancer biology Vol. 64; pp. 93 - 101
Main Authors Khan, Shaheen, Gerber, David E.
Format Journal Article
LanguageEnglish
Published England Elsevier Ltd 01.08.2020
Subjects
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
Autoimmunity
Immune checkpoint inhibitors
Immunotherapy
Toxicity and irAEs
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Summary: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.
ISSN:1044-579X
1096-3650
DOI:10.1016/j.semcancer.2019.06.012