Augment proteasome inhibitor efficacy activates CD8+T cell-mediated antitumor immunity in breast cancer

文献类型： 外文期刊

第一作者： Tang, Dongyang

作者： Tang, Dongyang;Lin, Shiqi;Zhou, Jingbo;Lei, Josh Haipeng;Shao, Fangyuan;Sun, Heng;Chu, Xiangpeng;Li, Ling;He, Lin;Qiao, Yunfeng;Xu, Xiaoling;Deng, Chu-Xia;Tang, Dongyang;Lin, Shiqi;Zhou, Jingbo;Lei, Josh Haipeng;Shao, Fangyuan;Sun, Heng;Chu, Xiangpeng;Li, Ling;He, Lin;Qiao, Yunfeng;Xu, Xiaoling;Deng, Chu-Xia;Zhou, Jingbo;Xu, Xiaoling;Deng, Chu-Xia

作者机构：

期刊名称：CELL REPORTS MEDICINE （ 影响因子：10.6； 五年影响因子：10.8 ）

ISSN： 2666-3791

年卷期： 2025 年 6 卷 7 期

页码：

收录情况： SCI

摘要： Although three proteasome inhibitors are used for liquid tumor treatment, their effectiveness against solid tumors remains inadequate. To address this issue, we employ a drug combination strategy and discover that ammonium tetrathiomolybdate (TM) and AMD3100 can sensitize solid cancer cell lines to proteasome inhibitors. Mechanistically, we find that TM and AMD3100 reduce proteasome activity by decreasing the protein level of PSMB5. This reduction occurs through the activation of the AMP-activated protein kinase (AMPK) pathway, which inhibits STAT3 phosphorylation. Notably, our in vivo studies reveal that drug combinations retard tumor growth dependent on CD8+ T cells. The combination of bortezomib with TM or AMD3100 induces cancer cell antigen presentation and the production of CCL5, which together stimulate the recruitment and generation of cytotoxic CD8+ T cells. This study identifies synergistic lethal pairs that enhance the effectiveness of bortezomib-centered therapy for breast cancer treatment in a way relied on intact immune system.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序