Work

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, 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, specifically the combination of scRNA-seq and scTCR/BCR-seq, to profile molecular and cellular changes in CIP tissues and matched noncancerous adjacent tissues from lung cancer patients. CIP patients exhibit disrupted immune homeostasis, marked by expansion of the CD8⁺ tissue-resident memory T cell population, 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. The treatment of lung cancer with checkpoint inhibitors is limited by the emergence of complications, including immunotherapy-induced pneumonitis (CIP). However, the immunological changes accompanying CIP are poorly characterized. Here, the authors perform single-cell analysis of CIP samples isolated from lung cancer patients and identify IFNγ-producing CD8 Tissue-resident T cells, IgG isotype class switching in B cells, and GSDME-mediated macrophage pyroptosis as central players in CIP.

Source: Nature Communications

DOI: 10.1038/s41467-025-66509-x