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In Frontiers in immunology ; h5-index 100.0

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.

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


PD-1, exosome, melanoma/tumor progression, metastasis, reprogramming, signalization pattern, stem cell