PB0751 - Platelets are integral components of the tumor microenvironment whose regulatory actions vary with the tumor type

Background: Whereas platelets are well known to promote the metastatic process, there is little evidence of their presence in the microenvironment (TME) of solid tumors. In addition, there are controversial data regarding the impact of platelets on primary tumor growth and it remains unclear whether platelets regulate immune cell infiltration in solid tumors as they do in other inflammatory sites.

Aims: We investigated whether platelets are present in the TME of solid tumors and participate in the regulation of its vascular and immune components.

Methods: The participation of platelets in the TME was assessed in 2 different mouse models of solid cancers (PyMT AT-3 breast cancer and B16F1 melanoma). The microenvironment of both types of solid tumor was characterized by immunohistology and semi-quantitative proteome profiler analysis. Platelet presence in the TME was investigated by immunohistology and intravital microscopy. The contribution of platelets to tumor growth, vessel density and integrity, and immune cell infiltration was determined using a model of chronic and profound thrombocytopenia based on the injection of a platelet-depleting antibody in mpl-/- mice.

Results: AT-3 mammary tumors were much more inflammatory and displayed a higher vessel density as compared to B16F1 melanoma. Firmly adherent platelets lining tumor vessels and perivascular platelets were systematically found in both types of tumor. “Platelet-like” cells displaying only a subset of platelet markers were additionally found in the stroma of AT-3 mammary tumors. Chronic and profound thrombocytopenia was associated with signs of severe endothelial degeneration and increased vascular leakage and bleeding only in AT-3 mammary tumors. Immune cell infiltration was increased in thrombocytopenic mice in both models of tumors while vascular density was unchanged between thrombocytopenic and WT mice.

Conclusion(s): Our findings indicate that platelets are integral components of the TME whose impact on tumor growth and TME modeling varies with the tumor type.