Uncoupling Therapeutic Efficacy from Immune-Related Adverse Events in Immune Checkpoint Blockade

Weilei Hu; Guosheng Wang; Yian Wang; Matthew J. Riese; Ming You

doi:10.1016/j.isci.2020.101580

Uncoupling Therapeutic Efficacy from Immune-Related Adverse Events in Immune Checkpoint Blockade

Weilei Hu, Guosheng Wang, Yian Wang, Matthew J. Riese, Ming You

Research output: Contribution to journal › Review article › peer-review

26 Scopus citations

Abstract

Immunotherapy with monoclonal antibodies targeting immune checkpoint molecules, including programmed death-1 (PD-1), PD ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen (CTLA)-4, has become prominent in the treatment of many types of cancer. However, a significant number of patients treated with immune checkpoint inhibitors (ICIs) develop immune-related adverse events (irAEs). irAEs can affect any organ system, and although most are clinically manageable, irAEs can result in mortality or long-term morbidity. Factors that can predict irAEs remain elusive. Understanding the etiology of ICI-induced irAEs and ways to limit these adverse events are needed. In this review, we provide basic science and clinical insights on the mechanisms responsible for ICI efficacy and ICI-induced irAEs. We further provide insights into approaches that may uncouple irAEs from the ability of ICIs to kill tumor cells.

Original language	English (US)
Article number	101580
Journal	iScience
Volume	23
Issue number	10
DOIs	https://doi.org/10.1016/j.isci.2020.101580
State	Published - Oct 23 2020

Keywords

Cancer
Clinical Medicine
Immunology

ASJC Scopus subject areas

General

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10.1016/j.isci.2020.101580

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title = "Uncoupling Therapeutic Efficacy from Immune-Related Adverse Events in Immune Checkpoint Blockade",

abstract = "Immunotherapy with monoclonal antibodies targeting immune checkpoint molecules, including programmed death-1 (PD-1), PD ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen (CTLA)-4, has become prominent in the treatment of many types of cancer. However, a significant number of patients treated with immune checkpoint inhibitors (ICIs) develop immune-related adverse events (irAEs). irAEs can affect any organ system, and although most are clinically manageable, irAEs can result in mortality or long-term morbidity. Factors that can predict irAEs remain elusive. Understanding the etiology of ICI-induced irAEs and ways to limit these adverse events are needed. In this review, we provide basic science and clinical insights on the mechanisms responsible for ICI efficacy and ICI-induced irAEs. We further provide insights into approaches that may uncouple irAEs from the ability of ICIs to kill tumor cells.",

keywords = "Cancer, Clinical Medicine, Immunology",

author = "Weilei Hu and Guosheng Wang and Yian Wang and Riese, {Matthew J.} and Ming You",

note = "Funding Information: This work was supported by National Cancer Institute grants R01CA223804 (M.Y.) and R01CA232433 (M.Y.). Conceptualization, W.H. G.W. Y.W. M.J.R. and M.Y.; Investigation, W.H. G.W. Y.W. M.J.R. and M.Y.; Writing – Original Draft, W.H. and G.W.; Writing – Review & Editing, Y.W. M.J.R. and M.Y.; Funding Acquisition, M.Y.; Supervision, M.Y. All authors revised and approved the final version of the manuscript. M.Y. is a co-founder of OncoImmune, Inc. No potential conflicts of interest were disclosed by other authors. Funding Information: This work was supported by National Cancer Institute grants R01CA223804 (M.Y.) and R01CA232433 (M.Y.). Publisher Copyright: {\textcopyright} 2020 The Authors",

year = "2020",

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AU - Hu, Weilei

AU - Wang, Guosheng

AU - Wang, Yian

AU - Riese, Matthew J.

AU - You, Ming

N1 - Funding Information: This work was supported by National Cancer Institute grants R01CA223804 (M.Y.) and R01CA232433 (M.Y.). Conceptualization, W.H. G.W. Y.W. M.J.R. and M.Y.; Investigation, W.H. G.W. Y.W. M.J.R. and M.Y.; Writing – Original Draft, W.H. and G.W.; Writing – Review & Editing, Y.W. M.J.R. and M.Y.; Funding Acquisition, M.Y.; Supervision, M.Y. All authors revised and approved the final version of the manuscript. M.Y. is a co-founder of OncoImmune, Inc. No potential conflicts of interest were disclosed by other authors. Funding Information: This work was supported by National Cancer Institute grants R01CA223804 (M.Y.) and R01CA232433 (M.Y.). Publisher Copyright: © 2020 The Authors

PY - 2020/10/23

Y1 - 2020/10/23

N2 - Immunotherapy with monoclonal antibodies targeting immune checkpoint molecules, including programmed death-1 (PD-1), PD ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen (CTLA)-4, has become prominent in the treatment of many types of cancer. However, a significant number of patients treated with immune checkpoint inhibitors (ICIs) develop immune-related adverse events (irAEs). irAEs can affect any organ system, and although most are clinically manageable, irAEs can result in mortality or long-term morbidity. Factors that can predict irAEs remain elusive. Understanding the etiology of ICI-induced irAEs and ways to limit these adverse events are needed. In this review, we provide basic science and clinical insights on the mechanisms responsible for ICI efficacy and ICI-induced irAEs. We further provide insights into approaches that may uncouple irAEs from the ability of ICIs to kill tumor cells.

AB - Immunotherapy with monoclonal antibodies targeting immune checkpoint molecules, including programmed death-1 (PD-1), PD ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen (CTLA)-4, has become prominent in the treatment of many types of cancer. However, a significant number of patients treated with immune checkpoint inhibitors (ICIs) develop immune-related adverse events (irAEs). irAEs can affect any organ system, and although most are clinically manageable, irAEs can result in mortality or long-term morbidity. Factors that can predict irAEs remain elusive. Understanding the etiology of ICI-induced irAEs and ways to limit these adverse events are needed. In this review, we provide basic science and clinical insights on the mechanisms responsible for ICI efficacy and ICI-induced irAEs. We further provide insights into approaches that may uncouple irAEs from the ability of ICIs to kill tumor cells.

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Uncoupling Therapeutic Efficacy from Immune-Related Adverse Events in Immune Checkpoint Blockade

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