Modulation of immune-responses by DSF/Cu enhances the anti-tumor effects of DTX for metastasis breast cancer

DSF/Cu 调节免疫反应可增强 DTX 对转移性乳腺癌的抗肿瘤作用

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作者:Jingtian Guo, Yuxiao Ma, Tiejun Tang, Zhengying Bian, Qianwen Li, Lei Tang, Zhuolan Li, Mengyuan Li, Liming Wang, Aizhong Zeng, Shihao Huang, Wei Guo

Abstract

Metastasis has been one of the most important causes of death from breast cancer, and chemotherapy remains the major option for metastatic breast cancer. However, drug resistance and higher toxicity from chemotherapy have been an obstacle for clinical practice, and the combination of chemotherapy with immunotherapy has emerged as a promising treatment strategy. Here, we describe a therapy based on the combination of disulfiram (DSF) and Cu2+ with widely used cytotoxic docetaxel (DTX). DSF/Cu-induced immunogenic cell death promoted the release of type I interferon and human monocyte-induced dendritic cell maturation, which established a foundation for the combination with chemotherapy. Consequently, the combination of DSF/Cu and DTX resulted in significantly more potent anti-tumor effects in 4T1-bearing mice than in single therapy. The present study has shed new light on combining DSF/Cu-induced immune responses with traditional chemotherapeutic agents to achieve greater benefits for patients with metastasis.

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