Regulation of dendritic cell maturation in osimertinib-treated lung adenocarcinoma patients

Abstract

Osimertinib (OSI), a third-generation tyrosine kinase inhibitor (TKI), efficiently benefits lung adenocarcinoma (LUAD) patients with epidermal growth factor receptor (EGFR) mutations. However, combined OSI and immune checkpoint inhibitor in EGFR-mutant patients increases the incidence of interstitial lung disease (ILD), although the mechanism is unknown. Here, we investigated the interaction between dendritic cells (DCs), a potential critical player in ILD, and OSI. Seventeen LUAD patients received TKI therapy, and only the OSI therapy group (N = 10) showed a significant increase in CD40 and CD83 on immature DCs (iDCs), and an elevated trend for both markers on mature DCs (mDCs) during short- and long-term OSI therapy. Our results indicated that OSI therapy may potentially activate DC functions, which might increase the potential immune toxicity when combined with onco-immunotherapy.

Keywords: CD40; CD83; Dendritic cells; Lung adenocarcinoma; Osimertinib.