Aqueous extract of Taxus chinensis var. mairei targeting CD47 enhanced antitumor effects in non-small cell lung cancer
Aqueous extract of Taxus chinensis var. mairei targeting CD47 enhanced antitumor effects in non-small cell lung cancer
复制标题
红豆杉的水提取物。
DOI：
10.1016/j.biopha.2022.113628
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发表时间：
2022-09-01
影响因子：
7.5
通讯作者：
Shju, Qijin
中科院分区：
文献类型：
--
作者：
Dai, Shuying;Liu, Yi;Shju, Qijin
免疫球蛋白CD47在恶性肿瘤细胞中过度表达，使其主要通过抑制巨噬细胞介导的吞噬作用来逃避宿主免疫。红豆杉mareii (TC) 具有高抗肿瘤功效、低毒性和显着的成本效益。然而，TC 水提取物 (AETC) 是否是介导抗肿瘤功效的免疫调节剂尚不清楚。在本研究中，我们旨在阐明 CD47 降解在非小细胞肺癌 (NSCLC) 细胞 AETC 治疗中的关键作用。开发了小鼠 Lewis 肺癌模型，以确定将 AETC 作为抗 CD47 抗体与抗 PD-1 联合给药是否可以协同抑制肿瘤生长并促进外周免疫反应。 AETC 治疗下调 NSCLC 细胞和 Lewis 肿瘤异种移植小鼠中的 CD47 水平。此外，治疗通过触发CD47泛素化和降解、促进巨噬细胞介导的肿瘤细胞吞噬作用以及激活CD8(+) T细胞来增强针对NSCLC的免疫力。本研究首次凭经验证明 AETC 作为免疫调节剂具有抗肿瘤特性。我们的研究结果表明 AETC 是肺癌治疗中一种有前途的替代疗法或辅助疗法。
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.