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节拍性紫杉醇通过改变肿瘤免疫微环境提高PD-1单克隆抗体在乳腺癌中的疗效。

Metronomic paclitaxel improves the efficacy of PD-1 monoclonal antibodies in breast cancer by transforming the tumor immune microenvironment.

作者信息

Chen Qian, Xia Rui, Zheng Weiwei, Zhang Luyao, Li Ping, Sun Xingwei, Shi Jianming

机构信息

Department of Oncology, The Affiliated Suzhou Hospital of Nanjing Medical University 242 Guangji Road, Suzhou 215008, Jiangsu, China.

Central Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University 242 Guangji Road, Suzhou 215008, Jiangsu, China.

出版信息

Am J Transl Res. 2020 Feb 15;12(2):519-530. eCollection 2020.

Abstract

The clinical efficacy of PD-1/PD-L1 monoclonal antibodies (mAbs) in triple-negative breast cancer (TNBC) is unsatisfactory. Immunotherapy combined with chemotherapy shows good therapeutic potential. Preclinical and clinical studies have shown that metronomic chemotherapy may stimulate anticancer immune responses. We aimed to verify whether metronomic paclitaxel (PTX, TAX) treatment can improve the efficacy of a PD-1 mAb in a TNBC mouse model and to explore the potential mechanism. After constructing the TNBC mouse model and treating with PD-1 mAb, metronomic PTX chemotherapy or combined therapy, the differences in the efficacy of each treatment group were compared and analyzed. Our findings suggested that the combination of metronomic PTX chemotherapy and PD-1 mAb produces a potent antitumor effect. Further experiments demonstrated that metronomic PTX chemotherapy changed the immune cell population in tumor tissues. These data suggest that metronomic PTX improves the efficacy of the PD-1 mAb in TNBC by transforming the tumor immune microenvironment, and these results provide strong evidence for the use of this treatment in TNBC patients in the future.

摘要

PD-1/PD-L1单克隆抗体(mAb)在三阴性乳腺癌(TNBC)中的临床疗效并不理想。免疫疗法联合化疗显示出良好的治疗潜力。临床前和临床研究表明,节拍化疗可能会刺激抗癌免疫反应。我们旨在验证节拍性紫杉醇(PTX,TAX)治疗是否能提高PD-1 mAb在TNBC小鼠模型中的疗效,并探索其潜在机制。构建TNBC小鼠模型并分别用PD-1 mAb、节拍性PTX化疗或联合治疗后,比较和分析各治疗组疗效的差异。我们的研究结果表明,节拍性PTX化疗与PD-1 mAb联合使用可产生强大的抗肿瘤作用。进一步的实验表明,节拍性PTX化疗改变了肿瘤组织中的免疫细胞群体。这些数据表明,节拍性PTX通过改变肿瘤免疫微环境提高了PD-1 mAb在TNBC中的疗效,这些结果为未来在TNBC患者中使用这种治疗方法提供了有力证据。

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