AUTHOR=Gyukity-Sebestyén Edina , Harmati Mária , Dobra Gabriella , Németh István B. , Mihály Johanna , Zvara Ágnes , Hunyadi-Gulyás Éva , Katona Róbert , Nagy István , Horváth Péter , Bálind Árpád , Szkalisity Ábel , Kovács Mária , Pankotai Tibor , Borsos Barbara , Erdélyi Miklós , Szegletes Zsolt , Veréb Zoltán J. , Buzás Edit I. , Kemény Lajos , Bíró Tamás , Buzás Krisztina TITLE=Melanoma-Derived Exosomes Induce PD-1 Overexpression and Tumor Progression via Mesenchymal Stem Cell Oncogenic Reprogramming JOURNAL=Frontiers in Immunology VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.02459 DOI=10.3389/fimmu.2019.02459 ISSN=1664-3224 ABSTRACT=

Recently, it has been described that programmed cell death protein 1 (PD-1) overexpressing melanoma cells are highly aggressive. However, until now it has not been defined which factors lead to the generation of PD-1 overexpressing subpopulations. Here, we present that melanoma-derived exosomes, conveying oncogenic molecular reprogramming, induce the formation of a melanoma-like, PD-1 overexpressing cell population (mMSCPD-1+) from naïve mesenchymal stem cells (MSCs). Exosomes and mMSCPD-1+ cells induce tumor progression and expression of oncogenic factors in vivo. Finally, we revealed a characteristic, tumorigenic signaling network combining the upregulated molecules (e.g., PD-1, MET, RAF1, BCL2, MTOR) and their upstream exosomal regulating proteins and miRNAs. Our study highlights the complexity of exosomal communication during tumor progression and contributes to the detailed understanding of metastatic processes.