Lymphocytes-Associated Extracellular Vesicles Activate Natural Killer Cells in HNSCC.

Small extracellular vesicles (sEVs) facilitate intercellular communication and play a pivotal role in tumor progression. Accumulated evidence has indicated the diversity of sEVs but with limited results revealing the landscape of heterogeneity of sEVs. The heterogeneity of cargo RNA in sEVs presents the different cell origins and indicates different functions. Here, we analyzed the heterogeneity of sEVs at droplet levels from single-cell RNA sequencing results of head and neck squamous cell carcinoma (HNSCC) with the previously reported algorithm SEVtras. With the sEVs secretion activity calculated by SEVtras, we also found that the T cells held the major role of sEVs secretion. In addition, we found these sEVs secreted by T cells increased the cytotoxic ability of natural killer cells (NK cells), which illustrated an indirect manner for the anti-tumor function of T cells. These results revealed the heterogeneity of cargo RNA of sEVs in HNSCC and underlined a sEVs-dependent manner in which T cells act on NK cells and anti-tumor immunity.