Uncovering the immune mechanisms underlying the emergence of immunotherapy-induced pneumonitis in lung cancer patients
Year: 2025
Type: article
Abstract: The clinical application of checkpoint inhibitors in lung cancer has been impeded by the emergence of immune-related adverse effects (irAE), such as pneumonitis. To date, the precise immune pathogenesis of immune checkpoint inhibitor-related pneumonitis (CIP) remains elusive. Here, we perform comprehensive single-cell analysis, combining scRNA-seq and scTCR/BCR-seq, to profile molecular and cellular changes in CIP and matched noncancerous adjacent tissues from lung cancer patients. CIP patients exhibit disrupted immune homeostasis, marked by an expansion of CD8⁺ tissue-resident memory T cells (Trm) with elevated IFNG expression and increased TCR clone sharing with other CD8⁺ T cells. We also identify increased IL-17A levels, robust IgG isotype class switching in B cells and GSDME-mediated macrophage pyroptosis as potential mechanisms involved in CIP. These findings provide valuable insights into the mechanisms underlying CIP and inform potential strategies for further intervention.
Author: Lin, Xinqing
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7089575567
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