Exploring the Immunomodulatory Potential of Pancreatic Cancer-Derived Extracellular Vesicles through Proteomic and Functional Analyses.

Autor: Piro A; Department of Pharmacy, G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy., Cufaro MC; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy.; Department of Medicine and Aging Sciences, G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy., Lanuti P; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy.; Department of Medicine and Aging Sciences, G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy., Brocco D; Department of Medical, Oral and Biotechnological Sciences, G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy., De Lellis L; Department of Pharmacy, G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy., Florio R; Department of Pharmacy, G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy., Pilato S; Department of Pharmacy, G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy.; UdA-TechLab, Research Center, G. d'Annunzio University of Chieti-Pescara, Via dei Vestini, 66100 Chieti, Italy., Pagotto S; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy.; Department of Medical, Oral and Biotechnological Sciences, G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy., De Fabritiis S; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy.; Department of Medicine and Aging Sciences, G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy., Vespa S; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy., Catitti G; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy.; Department of Medicine and Aging Sciences, G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy., Verginelli F; Department of Pharmacy, G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy.; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy., Simeone P; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy.; Department of Medicine and Aging Sciences, G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy., Pieragostino D; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy.; Department of Innovative Technologies in Medicine and Odontoiatry, G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy., Del Boccio P; Department of Pharmacy, G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy.; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy., Fontana A; Department of Pharmacy, G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy.; UdA-TechLab, Research Center, G. d'Annunzio University of Chieti-Pescara, Via dei Vestini, 66100 Chieti, Italy., Grassadonia A; Center for Advanced Studies and Technology (CAST), G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy.; Department of Innovative Technologies in Medicine and Odontoiatry, G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy., Di Ianni M; Department of Medicine and Aging Sciences, G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy.; Hematology Unit, Department of Oncology and Hematology, Santo Spirito Hospital, 65124 Pescara, Italy., Cama A; Department of Pharmacy, G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy., Veschi S; Department of Pharmacy, G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2024 May 08; Vol. 16 (10). Date of Electronic Publication: 2024 May 08.
DOI: 10.3390/cancers16101795
Abstrakt: Pancreatic cancer (PC) has a poor prognosis and displays resistance to immunotherapy. A better understanding of tumor-derived extracellular vesicle (EV) effects on immune responses might contribute to improved immunotherapy. EVs derived from Capan-2 and BxPC-3 PC cells isolated by ultracentrifugation were characterized by atomic force microscopy, Western blot (WB), nanoparticle tracking analysis, and label-free proteomics. Fresh PBMCs from healthy donors were treated with PC- or control-derived heterologous EVs, followed by flow cytometry analysis of CD8+ and CD4+ lymphocytes. The proteomics of lymphocytes sorted from EV-treated or untreated PBMCs was performed, and the IFN-γ concentration was measured by ELISA. Notably, most of the proteins identified in Capan-2 and BxPC-3 EVs by the proteomic analysis were connected in a single functional network ( p = 1 × 10 -16 ) and were involved in the "Immune System" (FDR: 1.10 × 10 -24 and 3.69 × 10 -19 , respectively). Interestingly, the treatment of healthy donor-derived PBMCs with Capan-2 EVs but not with BxPC-3 EVs or heterologous control EVs induced early activation of CD8+ and CD4+ lymphocytes. The proteomics of lymphocytes sorted from EV-treated PBMCs was consistent with their activation by Capan-2 EVs, indicating IFN-γ among the major upstream regulators, as confirmed by ELISA. The proteomic and functional analyses indicate that PC-EVs have pleiotropic effects, and some may activate early immune responses, which might be relevant for the development of highly needed immunotherapeutic strategies in this immune-cold tumor.
Databáze: MEDLINE
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