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Involvement of extracellular vesicles in the macrophage-tumor cell communication in head and neck squamous cell carcinoma Bellmunt Fontanet, Angela maria López-Puerto, Laura Lorente Guerrero, Juan Closa, Daniel [Bellmunt AM, Lorente J] Servei d’Otorrinolaringologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [López-Puerto L, Closa D] Department of Experimental Pathology, Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas (IIBB-CSIC), Barcelona, Spain. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain Vall d'Hebron Barcelona Hospital Campus Interacció cel·lular Macròfags Matriu extracel·lular PHENOMENA AND PROCESSES::Cell Physiological Phenomena::Cell Communication ANATOMY::Hemic and Immune Systems::Immune System::Mononuclear Phagocyte System::Hemic and Immune Systems::Immune System::Macrophages ANATOMY::Cells::Cellular Structures::Extracellular Space::Extracellular Vesicles FENÓMENOS Y PROCESOS::fenómenos fisiológicos celulares::comunicación celular ANATOMÍA::sistemas sanguíneo e inmunológico::sistema inmunológico::sistemas sanguíneo e inmunológico::sistema inmunológico::fagocitos::macrófagos ANATOMÍA::células::estructuras celulares::espacio extracelular::vesículas extracelulares Exosomes; Larynx cancer cells; Macrophages Exosomes; Cèl·lules cancerígenes de la laringe; Macròfags Exosomas; Células cancerosas de laringe; Macrófagos 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. This work was supported by a research grant from the Carlos III Institute of Health with reference FIS PI16/00060 (D.C.), co-funded with European Union ERDF funds (European Regional Development Fund). 2020-09-16T08:52:56Z 2020-09-16T08:52:56Z 2019-11-07 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Bellmunt AM, López-Puerto L, Lorente J, Closa D. Involvement of extracellular vesicles in the macrophage-tumor cell communication in head and neck squamous cell carcinoma. PLoS One. 2019 Nov 7;14(11):e0224710. 1932-6203 https://hdl.handle.net/11351/5265 10.1371/journal.pone.0224710 31697737 000532694400048 http://hdl.handle.net/11351/5265 eng PLoS One;14(11) https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224710 info:eu-repo/grantAgreement/ES/PE2013-2016/PI16%2F00060 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess application/pdf application/pdf Public Library of Science Scientia