Mechanisms of checkpoint inhibition induced adverse events

TY - JOUR

T1 - Mechanisms of checkpoint inhibition induced adverse events

AU - Urwyler, Pascal

AU - Earnshaw, Irina

AU - Bermudez, Maria

AU - Perucha, Esperanza

AU - Wu, Wing

AU - Ryan, Sarah

AU - Mcdonald, Louisa

AU - Karagiannis, Sophia N

AU - Taams, Leonie S

AU - Powell, Nicholas

AU - Cope, Andrew

AU - Papa, Sophie

N1 - Funding Information: The research was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) based at Guy?s and St Thomas? NHS Foundation Trust and King?s College London (IS- BRC-1215-20006) and the Cancer Research UK King?s Health Partners Centre at King?s College London. The authors are solely responsible for study design, data collection, analysis, decision to publish and preparation of the paper. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. No funding was obtained for the writing of this manuscript. Publisher Copyright: © 2020 British Society for Immunology

PY - 2020/4/16

Y1 - 2020/4/16

N2 - Immune checkpoint inhibition has revolutionized the treatment of several solid cancers, most notably melanoma and non-small-cell lung cancer (NSCLC). Drugs targeting cytotoxic T lymphocyte antigen (CTLA)-4 and programmed cell death 1 (PD-1) have made their way into routine clinical use; however, this has not been without difficulties. Stimulation of the immune system to target cancer has been found to result in a reduction of self-tolerance, leading to the development of adverse effects that resemble autoimmunity. These adverse effects are erratic in their onset and severity and can theoretically affect any organ type. Several mechanisms for immune-related toxicity have been investigated over recent years; however, no consensus on the cause or prediction of toxicity has been reached. This review seeks to examine reported evidence for possible mechanisms of toxicity, methods for prediction of those at risk and a discussion of future prospects within the field.

AB - Immune checkpoint inhibition has revolutionized the treatment of several solid cancers, most notably melanoma and non-small-cell lung cancer (NSCLC). Drugs targeting cytotoxic T lymphocyte antigen (CTLA)-4 and programmed cell death 1 (PD-1) have made their way into routine clinical use; however, this has not been without difficulties. Stimulation of the immune system to target cancer has been found to result in a reduction of self-tolerance, leading to the development of adverse effects that resemble autoimmunity. These adverse effects are erratic in their onset and severity and can theoretically affect any organ type. Several mechanisms for immune-related toxicity have been investigated over recent years; however, no consensus on the cause or prediction of toxicity has been reached. This review seeks to examine reported evidence for possible mechanisms of toxicity, methods for prediction of those at risk and a discussion of future prospects within the field.

KW - CTLA-4

KW - PD-1

KW - cancer

KW - checkpoint

KW - immunotherapy

UR - http://www.scopus.com/inward/record.url?scp=85083360193&partnerID=8YFLogxK

U2 - 10.1111/cei.13421

DO - 10.1111/cei.13421

M3 - Article

C2 - 31989585

SN - 0009-9104

VL - 200

SP - 141

EP - 154

JO - Clin Exp Immunol

JF - Clin Exp Immunol

IS - 2

ER -