Autoimmunity, checkpoint inhibitor therapy and immune-related adverse events: A review

Research output: Contribution to journalReview article

4 Citations (Scopus)

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.

Original languageEnglish (US)
JournalSeminars in Cancer Biology
DOIs
StatePublished - Jan 1 2019

Fingerprint

Autoimmunity
Neoplasms
Epigenomics
Autoimmune Diseases
Immune System
Therapeutics
Biomarkers
T-Lymphocytes
Research

Keywords

  • Autoimmunity
  • Immune checkpoint inhibitors
  • Immunotherapy
  • Toxicity and irAEs

ASJC Scopus subject areas

  • Cancer Research

Cite this

@article{6c44d27f9557428f85e9bb9862255f63,
title = "Autoimmunity, checkpoint inhibitor therapy and immune-related adverse events: A review",
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.",
keywords = "Autoimmunity, Immune checkpoint inhibitors, Immunotherapy, Toxicity and irAEs",
author = "Shaheen Khan and Gerber, {David E}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.semcancer.2019.06.012",
language = "English (US)",
journal = "Seminars in Cancer Biology",
issn = "1044-579X",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Autoimmunity, checkpoint inhibitor therapy and immune-related adverse events

T2 - A review

AU - Khan, Shaheen

AU - Gerber, David E

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - Autoimmunity

KW - Immune checkpoint inhibitors

KW - Immunotherapy

KW - Toxicity and irAEs

UR - http://www.scopus.com/inward/record.url?scp=85069837556&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069837556&partnerID=8YFLogxK

U2 - 10.1016/j.semcancer.2019.06.012

DO - 10.1016/j.semcancer.2019.06.012

M3 - Review article

C2 - 31330185

AN - SCOPUS:85069837556

JO - Seminars in Cancer Biology

JF - Seminars in Cancer Biology

SN - 1044-579X

ER -