Abstract
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.
Highlights
Tumours constitute unique microenvironments where various blood cells and factors are exposed as a result of leaky vasculature
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
To better observe the thrombin distribution in tumours, frozen sections of B16F10 melanoma and kidney were prepared for confocal microscopy
Summary
Tumours constitute unique microenvironments where various blood cells and factors are exposed as a result of leaky vasculature. 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. As a downstream effector of interferon-gamma (IFN-γ), the antitumour activity of IP10 has been previously demonstrated in several cancer types, such as breast, B Burkitt lymphoma and myeloma[21,22,23] The interaction of this chemokine with endothelial cells leads to angiostatic responses[24,25]
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