Platelet-cytokine Complex Suppresses Tumour Growth by Exploiting Intratumoural Thrombin-dependent Platelet Aggregation.
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.
Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
Yu-Tung
YT
Li
Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
Tomoyuki
T
Nishikawa
Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
Yasufumi
Y
Kaneda
D000818:Animals; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism*; D054357:Chemokine CXCL10 / Q000008:administration & dosage*; D004195:Disease Models, Animal; D007262:Infusions, Intravenous; D008545:Melanoma / Q000473:pathology / Q000628:therapy*; D008810:Mice, Inbred C57BL; D010974:Platelet Aggregation; D013917:Thrombin / Q000378:metabolism*
D054357:Chemokine CXCL10; D013917:Thrombin