Platelets are critical to hemostatic and immunological function, and are key players in cancer progression, metastasis, and cancer-related thrombosis. Platelets interact with immune cells to stimulate anti-tumor responses and can be activated by immune cells and tumor cells. Platelet activation can lead to complex interactions between platelets and tumor cells. Platelets facilitate cancer progression and metastasis by: (1) forming aggregates with tumor cells; (2) inducing tumor growth, epithelial-mesenchymal transition, and invasion; (3) shielding circulating tumor cells from immune surveillance and killing; (4) facilitating tethering and arrest of circulating tumor cells; and (5) promoting angiogenesis and tumor cell establishment at distant sites. Tumor cell-activated platelets also predispose cancer patients to thrombotic events. Tumor cells and tumor-derived microparticles lead to thrombosis by secreting procoagulant factors, resulting in platelet activation and clotting. Platelets play a critical role in cancer progression and thrombosis, and markers of platelet-tumor cell interaction are candidates as biomarkers for cancer progression and thrombosis risk.

Platelet-leukocyte aggregates (PLAs) are associated with increased thrombosis risk. The influence of PLA formation is especially important for cancer patients, since thrombosis accounts for approximately 10% of cancer-associated deaths. Our objective was to characterize and quantify PLAs in whole blood samples from lung cancer patients compared to healthy volunteers with the intent to analyze PLA formation in the context of lung cancer-associated thrombosis. Consenting lung cancer patients (57) and healthy volunteers (56) were enrolled at the Dana Cancer Center at the University of Toledo Health Science Campus. Peripheral blood samples were analyzed by flow cytometry. Patient medical history was reviewed through electronic medical records. Most importantly, we found lung cancer patients to have higher percentages of platelet-T cell aggregates (PTCAs) than healthy volunteers among both CD4+ T lymphocyte and CD8+ T lymphocyte populations. Our findings demonstrate that characterization of PTCAs may have clinical utility in differentiating lung cancer patients from healthy volunteers and stratifying lung cancer patients by history of thrombosis.

This study aimed to characterize the role of platelet-leukocyte aggregation in lung cancer patients in context of history of thrombosis. Whole blood from lung cancer patients and healthy volunteers was labeled with fluorescently-conjugated antibodies, then fixed prior to flow cytometry. Platelet-leukocyte aggregates were quantified by detecting the number of platelets within all leukocyte-positive events. Platelet-CD4 T cell and platelet-CD8 T cell aggregates were both significantly increased in lung cancer patients (both p < 0.0001). Lung cancer patients had significantly more CD4 and CD8 T cells aggregated with activated platelets compared to healthy volunteers (p < 0.01 and p < 0.001, respectively). Lung cancer patients were then separated into groups based on history of thrombosis: No previous thrombosis, arterial thrombotic event (ATE), and venous thromboembolism (VTE). ATE patients had significantly more CD8 T cells aggregated with platelets than patients with no history of thrombosis (p < 0.05). VTE patients had significantly higher expression of platelet activation markers in CD4 and CD8 T cell aggregates than patients with no history of thrombosis (p < 0.01 and p < 0.001, respectively) and ATE patients (p < 0.05 and p < 0.001, respectively). Platelet-T cell aggregates were significantly increased in lung cancer patients compared to healthy volunteers, and platelet activation within aggregates was significantly correlated with history of VTE in patients with lung cancer. These findings indicate that interactions between platelets and T cells in cancer patients may contribute to a procoagulant phenotype.