Aqueous extract of Taxus chinensis var. mairei targeting CD47 enhanced antitumor effects in non-small cell lung cancer - 10/09/22
Abstract |
Immunoglobulin protein CD47 is overexpressed in malignant tumor cells, allowing them to evade host immunity mainly by inhibiting macrophage-mediated phagocytosis. Taxus chinensis var. mairei (TC) exhibits high antitumor efficacy with low toxicity and notable cost-effectiveness. However, it is unknown whether aqueous extract of TC (AETC) is an immunomodulator that mediates antitumor efficacy. In this study, we aimed to elucidate the critical role of CD47 degradation in the treatment of AETC in non-small cell lung cancer (NSCLC) cells. A mouse Lewis lung carcinoma model was developed to determine whether the administration of AETC, as an anti-CD47 antibody, in combination with anti-PD-1 could synergistically inhibit tumor growth and promote a peripheral immune response. AETC treatment downregulated CD47 levels in NSCLC cells and Lewis tumor xenograft mice. Furthermore, treatment enhanced immunity against NSCLC by triggering CD47 ubiquitination and degradation, promoting macrophage-mediated tumor cell phagocytosis, and activating CD8+ T cells. The present study empirically demonstrated, for the first time, that AETC exerts antitumor properties as an immunomodulator. Our findings present AETC as a promising alternative or adjuvant treatment in lung cancer therapy.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | CD47 helps tumors evade host immunity by inhibiting macrophage-mediated phagocytosis. |
• | Aqueous extract of Taxus chinensis var. mairei has high antitumor efficacy on NSCLC. |
• | AETC is a naturally occurring CD47 inhibitor that triggers its ubiquitin degradation. |
• | AETC improves peripheral immune responses to LUAD and sensitizes pembrolizumab. |
Abbreviations : AETC, APC, BCA, CSC, CHX, ECL, FBS, HPLC, ICI, IHC, LLC, LUAD, MHC, NSCLC, PBS, PBST, PD-L1, PM, PVDF, RIPA, SIRPα, STR, TC, TCM, TME, Treg, UPS
Keywords : CD47, Macrophage, Non-small cell lung cancer, Taxus chinensis var. mairei
Plan
Vol 154
Article 113628- octobre 2022 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?