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Regulation of dendritic cell maturation in osimertinib-treated lung adenocarcinoma patients
Ming-Fang Wu1, Ya-Hsuan Chang2, Hsuan-Yu Chen3
1Graduate Institute of Toxicology, National Taiwan University College of Medicine, Taipei, Taiwan; Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
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.
Insights
Osimertinib (OSI) therapy may activate dendritic cells (DCs) in lung adenocarcinoma (LUAD) patients. This activation could increase immune toxicity when OSI is combined with immune checkpoint inhibitors, potentially contributing to interstitial lung disease (ILD).
Area of Science:
- Oncology
- Immunology
- Pulmonology
Background:
- Osimertinib (OSI), a third-generation tyrosine kinase inhibitor (TKI), is effective for EGFR-mutant lung adenocarcinoma (LUAD).
- Combining OSI with immune checkpoint inhibitors in EGFR-mutant LUAD patients increases interstitial lung disease (ILD) incidence, with an unknown mechanism.
- Dendritic cells (DCs) are investigated as potential key players in OSI-induced ILD.
Purpose of the Study:
- To investigate the interaction between dendritic cells (DCs) and Osimertinib (OSI) in EGFR-mutant lung adenocarcinoma (LUAD) patients.
- To explore whether OSI therapy influences DC activation markers.
Main Methods:
- Seventeen LUAD patients receiving TKI therapy were analyzed.
- DC activation markers (CD40 and CD83) on immature DCs (iDCs) and mature DCs (mDCs) were measured in patients treated with OSI.
- Comparisons were made between OSI therapy groups and other TKI groups.
Main Results:
- Osimertinib (OSI) therapy significantly increased CD40 and CD83 expression on immature dendritic cells (iDCs).
- An elevated trend for CD40 and CD83 on mature dendritic cells (mDCs) was observed during both short- and long-term OSI therapy.
- These changes were specific to the OSI treatment group.
Conclusions:
- Osimertinib (OSI) therapy may activate dendritic cell (DC) functions in lung adenocarcinoma (LUAD) patients.
- Activated DCs could contribute to increased immune toxicity when OSI is combined with immune checkpoint inhibitors.
- This DC activation mechanism may play a role in the development of interstitial lung disease (ILD).
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