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Background: Exosomes are cell-derived vesicles that mediate cellular communication in health and multiple diseases, including cancer. However, its role in head and neck cancer has been poorly defined. Here, we investigated the relevance of exosomes in the signaling between larynx cancer cells and macrophages. Methods: Exosomes from THP1 macrophages and BICR18 cells (a larynx squamous cell carcinoma cell line) were purified and their role in the cancer cell migration, macrophage phenotype and immunosuppressive activity was evaluated. The activation of STAT3 signal transduction in macrophages in response to exosomes obtained from cancer cells was also evaluated. Results: Macrophages foster the cancer cell migration and this effect is mediated by exosome signaling. On the other hand, exosomes also induce the expression of IL-10 in macrophages and PD-L1 in cancer cells, thus resulting in the promotion of an immunosuppressive environment. Moreover, we observed that the effects induced in cancer cells are mediated by the exosome-depending activation of STAT-3 signal transduction pathway. Conclusions: Our study indicates that exosomes released by both macrophages and cancer cells plays a critical role in tumor progression in larynx cancer and might be a potential target for therapeutic intervention in head and neck cancer. [ABSTRACT FROM AUTHOR]