Pulmonary toxicity of immune checkpoint immunotherapy
Mohammad I. Ghanbar, Karthik Suresh
Mohammad I. Ghanbar, Karthik Suresh
Published January 16, 2024
Citation Information: J Clin Invest. 2024;134(2):e170503. https://doi.org/10.1172/JCI170503.
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Review

Pulmonary toxicity of immune checkpoint immunotherapy

Abstract

Cancer remains a leading cause of mortality on a global scale. Lung cancer, specifically non–small cell lung cancer (NSCLC), is a prominent contributor to this burden. The management of NSCLC has advanced substantially in recent years, with immunotherapeutic agents, such as immune checkpoint inhibitors (ICIs), leading to improved patient outcomes. Although generally well tolerated, the administration of ICIs can result in unique side effects known as immune-related adverse events (irAEs). The occurrence of irAEs involving the lungs, specifically checkpoint inhibitor pneumonitis (CIP), can have a profound effect on both future therapy options and overall survival. Despite CIP being one of the more common serious irAEs, limited treatment options are currently available, in part due to a lack of understanding of the underlying mechanisms involved in its development. In this Review, we aim to provide an overview of the epidemiology and clinical characteristics of CIP, followed by an examination of the emerging literature on the pathobiology of this condition.

Authors

Mohammad I. Ghanbar, Karthik Suresh

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Figure 1

Immune checkpoint biology.

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Immune checkpoint biology. (A) T cell activation is initiated by interac...
(A) T cell activation is initiated by interacting via its T cell receptor with APCs that present offending antigens. A costimulatory signal is additionally required on the T cell CD28 receptor for full activation. Upon activation, CTLA-4 and PD-1 are expressed on the cell surface. (B) CD28 costimulation can be inhibited by CTLA-4, leading to T cell dysfunction. CTLA-4 expression can be enhanced by the tumor microenvironment (TME). Both of these steps occur at the level of the lymphoid organs. (C) Stimulation of the PD-1 receptor by tumor-expressed PD-L1 can render activated T cells dormant, inhibiting immune responses against cancer cells. These mechanisms can be overcome with specific antibodies against the receptors (CTLA-4, PD-1) or ligands (PD-L1).