Immunobiology of Platelets

Platelets are small cells of great importance in numerous pathophysiological processes such as thrombosis, hemorrhage, and wound healing. Beyond the canonical platelets functions these anucleate tiny cells also serve critical roles in various processes, including inflammation, immune regulation, angiogenesis, metastasis, tumor grow and conditions like coronary disease, stroke, and diabetes mellitus.

In recent years, research has demonstrated that platelets dynamically interact with tumor cells, facilitating its survival and proliferation. These interactions also trigger platelet hypersensitivity or activation. Upon activation, platelets can release various pro-survival, pro-angiogenic, and immune-modulating factors, regardless of direct contact with the tumor. This activity significantly contributes to the formation and sustenance of both the primary tumor microenvironment and the microenvironment of metastatic tumors.

In our lab, we hypothesize that circulating conditioned platelets interact with the tumor microenvironment (TME), altering its immunosuppressive, metabolic, and angiogenic characteristics.  In particular, our research focuses on investigating the interactions between MDSC-platelets, T cell-platelets, and DC-platelets within the tumor microenvironment (TME). We are introducing a novel therapeutic approach based on the concept that reprogramming platelets will ultimately reduce the immunosuppressive characteristics of the TME, potentially leading to improved effectiveness of checkpoint immunotherapies.

On the other hand, evidence suggests that activated platelets play a crucial role in chronic inflammatory conditions like diabetes, atherosclerosis, and obesity, shifting the conventional understanding of metabolic and hemodynamic changes as the main causes of these diseases. Platelets from these patients show increased aggregation rates in response to pro-thrombotic agonists. This highlights the potential impact of inflammatory processes, including platelet activation, on the tumor microenvironment and tumor outcomes. The precise role of preconditioned activated platelets in the tumor microenvironment, and their potential as targets for anti-tumor therapy, remains unclear and requires further investigation.

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