Immune checkpoint inhibitor-associated toxicity in advanced non-small cell lung cancer: An updated understanding of risk factors

Xiangxiao Hu; Lina Wang; Bin Shang; Junren Wang; Jian Sun; Bin Liang; Lili Su; Wenjie You; Shujuan Jiang

doi:10.3389/fimmu.2023.1094414

Immune checkpoint inhibitor-associated toxicity in advanced non-small cell lung cancer: An updated understanding of risk factors

Front Immunol. 2023 Mar 6:14:1094414. doi: 10.3389/fimmu.2023.1094414. eCollection 2023.

Authors

Xiangxiao Hu^{1

2

3}, Lina Wang^{1

2

3

4}, Bin Shang⁵, Junren Wang^{1

2

3}, Jian Sun^{1

2

3}, Bin Liang^{1

2

3}, Lili Su^{1

2

3}, Wenjie You^{1

2

3

6}, Shujuan Jiang^{1

2

3}

Affiliations

¹ Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, China.
² Shandong Key Laboratory of Infectious Respiratory Disease, Jinan, China.
³ Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
⁴ Department of Respiratory and Critical Care Medicine, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁵ Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
⁶ Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

Abstract

Immune checkpoint inhibitors (ICIs), such as programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies, etc, have revolutionized cancer treatment strategies, including non-small cell lung cancer (NSCLC). While these immunotherapy agents have achieved durable clinical benefits in a subset of NSCLC patients, they bring in a variety of immune-related adverse events (irAEs), which involve cardiac, pulmonary, gastrointestinal, endocrine and dermatologic system damage, ranging from mild to life-threatening. Thus, there is an urgent need to better understand the occurrence of irAEs and predict patients who are susceptible to those toxicities. Herein, we provide a comprehensive review of what is updated about the clinical manifestations, mechanisms, predictive biomarkers and management of ICI-associated toxicity in NSCLC. In addition, this review also provides perspective directions for future research of NSCLC-related irAEs.

Keywords: combined immunotherapies; immune checkpoint inhibitor; immune-related toxicity; non-small cell lung cancer; predictive biomarker.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal / adverse effects
Carcinoma, Non-Small-Cell Lung*
Humans
Immune Checkpoint Inhibitors / adverse effects
Lung Neoplasms*
Risk Factors

Substances

Immune Checkpoint Inhibitors
Antibodies, Monoclonal

Grants and funding

This work was supported in part by grant 81902325 from the National Natural Science Foundation of China, grants ZR2020MH005 and ZR2021ZD35 from the Shandong Provincial Natural Science Foundation (China), grants 202019201 and 202225051 from the Jinan Science and Technology Plan Project (China), grant 2019GSF107051 from the Key Research and Development Plan of Shandong Province (China), and grant 2021GXRC018 from Jinan Talent Development Special Foundation (China).