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  • 标题:Perfluorocarbon nanoparticle-mediated platelet inhibition promotes intratumoral infiltration of T cells and boosts immunotherapy
  • 本地全文:下载
  • 作者:Zaigang Zhou ; Zaigang Zhou ; Baoli Zhang
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2019
  • 卷号:116
  • 期号:24
  • 页码:11972-11977
  • DOI:10.1073/pnas.1901987116
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Cancer immunotherapy can stimulate and enhance the ability of the immune system to recognize, arrest, and eliminate tumor cells. Immune checkpoint therapies (e.g., PD-1/PD-L1) have shown an unprecedented and durable clinical response rate in patients among various cancer types. However, a large fraction of patients still does not respond to these checkpoint inhibitors. The main cause of this phenomenon is the limited T-cell infiltration in tumors. Therefore, additional strategies to enhance T-cell trafficking into tumors are urgently needed to improve patients’ immune responses. In this study, we screened an array of perfluorocarbon compounds, reporting that albumin-based perfluorotributylamine nanoparticles (PFTBA@Alb) can effectively increase the permeability of tumor blood vessels, and no distinct side effects were found on normal blood vessels. After i.v. administration of PFTBA@Alb, the number of tumor-infiltrating CD8+ and CD4+ T cells showed an obvious rising trend. More important, a striking tumor inhibition rate, reaching nearly 90%, was observed when combining PFTBA@Alb with anti–PD-L1 antibody. These findings suggest that PFTBA@Alb can be regarded as an enhancer for anti–PD-L1 immunotherapy.
  • 关键词:immunotherapy ; platelet inhibition ; immune cell infiltration
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