化学免疫疗法
三阴性乳腺癌
肿瘤微环境
免疫系统
乳腺癌
内科学
化疗
癌症研究
阿霉素
医学
免疫检查点
CD8型
药理学
免疫学
癌症
免疫疗法
作者
Xianzu Gong,Chao Zheng,Ying Cai,Wen Zhang,Binyu Zhu,Rong Rong,Ying Kong,Yuan Zhang,Jian Wang,Yaping Li,Pengcheng Zhang
标识
DOI:10.1016/j.jconrel.2024.01.064
摘要
Adenosine (ADO) is a common chemotherapy-associated immune checkpoint that hinders anti-tumor immunity-mediated efficacy of chemotherapy. Herein, we created a synthetic high-density lipoprotein (sHDL) by co-assembly of a doxorubicin (DOX)-apolipoprotein A1 mimetic peptide conjugate, PSB-603 (an A2BR inhibitor), phospholipid, and cholesterol oleate with a microfluidic-based method. The obtained DP-sHDL showed a self-promoted drug delivery to cancer cells via remodeling tumor microenvironment. DP-sHDL could trigger the release of ATP from cancer cells and inhibit its conversion into ADO. Consequently, DP-sHDL, while increasing immunogenic cell death, reduced intratumoral ADO levels by 58%. This treatment improved both the density and activity of CD8+ T cells as well as NK cells and relieved the immunosuppressive microenvironment, and led to a substantial inhibition of 4T1 tumor growth, thereby extending the survival of mice. The efficacy of DP-sHDL could be further improved when used in combination with immune checkpoint blockade therapy. We envision that this platform provides a simple yet promising strategy to enhance anti-tumor response of chemotherapy by relieving treatment-associated immunosuppression.
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