Chidamide improves gefitinib treatment outcomes in NSCLC by attenuating recruitment and immunosuppressive function of myeloid-derived suppressor cells - 22/03/24
Abstract |
Clinical resistance to EGFR tyrosine kinase inhibitors in non-small-cell lung cancer (NSCLC) remains a significant challenge. Recent studies have indicated that the number of myeloid-derived suppressor cells (MDSCs) increases following gefitinib treatment, correlating with a poor patient response in NSCLC. Our study revealed that gefitinib treatment stimulates the production of CCL2, which subsequently enhances monocyte (M)-MDSC migration to tumor sites. Chidamide, a selective inhibitor of the histone deacetylase subtype, counteracted the gefitinib-induced increase in CCL2 levels in tumor cells. Additionally, chidamide down-regulated the expression of CCR2 in M-MDSCs, inhibiting their migration. Furthermore, chidamide attenuated the immunosuppressive function of M-MDSCs both alone and in combination with gefitinib. Chidamide also alleviated tumor immunosuppression by reducing the number of M-MDSCs in LLC-bearing mice, thereby enhancing the antitumor efficacy of gefitinib. In conclusion, our findings suggest that chidamide can improve gefitinib treatment outcomes, indicating that MDSCs are promising targets in NSCLC.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Gefitinib boosts tumor CCL2 expression and enhances M-MDSC migration to tumors. |
• | Chidamide counters the gefitinib-induced increase in CCL2 expression in tumors. |
• | Chidamide inhibits CCR2 expression on M-MDSCs and suppresses cell migration. |
• | Chidamide mitigates M-MDSC immunosuppression, either alone or with gefitinib. |
• | Chidamide reduces M-MDSC levels in LLC-bearing mice, boosting gefitinib efficacy. |
Keywords : Chidamide, Gefitinib, MDSC, NSCLC, CCL2/CCR2
Plan
Vol 173
Article 116306- avril 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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