Our experiments revealed that co-incubation of HNSCC cell line-derived EVs with PLTs induces robust PLT aggregation and activation as evidenced by notable increase in aggregation as measured by aggregometry, enhanced secretion of alpha and dense granules, which is quantified by elevated levels of ATP and CCL5 in ELISA, and a marked increase in the expression of surface activation markers, specifically CD62P and CD63. Here, CCL5 is linked to head and neck squamous cell carcinoma.