Platelet-cytokine Complex Suppresses Tumour Growth by Exploiting Intratumoural Thrombin-dependent Platelet Aggregation.
Platelet-cytokine Complex Suppresses Tumour Growth by Exploiting Intratumoural Thrombin-dependent Platelet Aggregation.
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DOI：
10.1038/srep25077
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发表时间：
2016-04-27
影响因子：
4.6
通讯作者：
Kaneda Y
中科院分区：
文献类型：
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作者：
Li YT;Nishikawa T;Kaneda Y
肿瘤构成了独特的微环境，其中各种血细胞和因子由于血管渗漏而暴露。在本研究中，我们报告说，凝血酶富集在B16 F10黑色素瘤导致血小板聚集，并利用这一属性管理的抗癌细胞因子，干扰素-γ诱导蛋白10（IP 10），通过形成血小板-IP 10复合物。当静脉输注时，复合物到达肿瘤中的血小板微聚集体。复合物诱导的反应仅为免疫介导的，未观察到肿瘤细胞毒性。该复合物在体内抑制了小鼠黑色素瘤的生长，而血小板和复合物都抑制了FoxP 3+调节性T细胞在肿瘤中的积累。这些结果表明，B16 F10肿瘤中的凝血酶依赖性血小板聚集将血小板定义为递送抗癌细胞因子并提供特定治疗益处的载体。
Tumours constitute unique microenvironments where various blood cells and factors are exposed as a result of leaky vasculature. In the present study, we report that thrombin enrichment in B16F10 melanoma led to platelet aggregation, and this property was exploited to administer an anticancer cytokine, interferon-gamma induced protein 10 (IP10), through the formation of a platelet-IP10 complex. When intravenously infused, the complex reached platelet microaggregates in the tumour. The responses induced by the complex were solely immune-mediated, and tumour cytotoxicity was not observed. The complex suppressed the growth of mouse melanoma in vivo, while both platelets and the complex suppressed the accumulation of FoxP3+ regulatory T cells in the tumour. These results demonstrated that thrombin-dependent platelet aggregation in B16F10 tumours defines platelets as a vector to deliver anticancer cytokines and provide specific treatment benefits.