Aqueous extract of Taxus chinensis var. mairei targeting CD47 enhanced antitumor effects in non-small cell lung cancer

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.