Macrophage NLRP3 activation and IL-1β release drive osimertinib-induced antitumor immunity.

ABSTRACT:

Background

Despite the clinical efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC), patient outcomes vary even among those with identical EGFR mutations. This study investigates whether osimertinib, a third-generation EGFR-TKI, activates the nucleotide-binding oligomerization domain-like receptor protein-3 (NLRP3) inflammasome in macrophages to drive antitumor immunity and explores its mechanistic basis.

Methods

Using bone marrow-derived macrophages from wild-type and gene-deficient mice, human peripheral blood mononuclear cells, and a Lewis lung cancer murine model, we assessed osimertinib-induced NLRP3 inflammasome activation, interleukin (IL)-1β secretion, pyroptosis, and tumor microenvironment (TME) r

SUBMITTER: Yu H 

PROVIDER: S-EPMC12506461 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature