免疫疗法
CD8型
癌症研究
医学
血小板
环磷酰胺
肿瘤微环境
祖细胞
癌症免疫疗法
细胞毒性T细胞
免疫学
巨核细胞
免疫系统
内科学
化学
干细胞
生物
化疗
细胞生物学
体外
生物化学
作者
Xudong Zhang,Jinqiang Wang,Zhaowei Chen,Quanyin Hu,Chao Wang,Junjie Yan,Gianpietro Dotti,Peng Huang,Zhen Gu
出处
期刊:Nano Letters
[American Chemical Society]
日期:2018-07-31
卷期号:18 (9): 5716-5725
被引量:182
标识
DOI:10.1021/acs.nanolett.8b02321
摘要
Radical surgery still represents the treatment choice for several malignancies. However, local and distant tumor relapses remain the major causes of treatment failure, indicating that a postsurgery consolidation treatment is necessary. Immunotherapy with checkpoint inhibitors has elicited impressive clinical responses in several types of human malignancies and may represent the ideal consolidation treatment after surgery. Here, we genetically engineered platelets from megakaryocyte (MK) progenitor cells to express the programmed cell death protein 1 (PD-1). The PD-1 platelet and its derived microparticle could accumulate within the tumor surgical wound and revert exhausted CD8+ T cells, leading to the eradication of residual tumor cells. Furthermore, when a low dose of cyclophosphamide (CP) was loaded into PD-1-expressing platelets to deplete regulatory T cells (Tregs), an increased frequency of reinvigorated CD8+ lymphocyte cells was observed within the postsurgery tumor microenvironment, directly preventing tumor relapse.
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