Piro, A.; Cufaro, M.C.; Lanuti, P.; Brocco, D.; De Lellis, L.; Florio, R.; Pilato, S.; Pagotto, S.; De Fabritiis, S.; Vespa, S.; Catitti, G.; Verginelli, F.; Simeone, P.; Pieragostino, D.; Del Boccio, P.; Fontana, A.; Grassadonia, A.; Di Ianni, M.; Cama, A.; Veschi, S. Exploring the Immunomodulatory Potential of Pancreatic Cancer-Derived Extracellular Vesicles through Proteomic and Functional Analyses. Cancers2024, 16, 1795.
Piro, A.; Cufaro, M.C.; Lanuti, P.; Brocco, D.; De Lellis, L.; Florio, R.; Pilato, S.; Pagotto, S.; De Fabritiis, S.; Vespa, S.; Catitti, G.; Verginelli, F.; Simeone, P.; Pieragostino, D.; Del Boccio, P.; Fontana, A.; Grassadonia, A.; Di Ianni, M.; Cama, A.; Veschi, S. Exploring the Immunomodulatory Potential of Pancreatic Cancer-Derived Extracellular Vesicles through Proteomic and Functional Analyses. Cancers 2024, 16, 1795.
Piro, A.; Cufaro, M.C.; Lanuti, P.; Brocco, D.; De Lellis, L.; Florio, R.; Pilato, S.; Pagotto, S.; De Fabritiis, S.; Vespa, S.; Catitti, G.; Verginelli, F.; Simeone, P.; Pieragostino, D.; Del Boccio, P.; Fontana, A.; Grassadonia, A.; Di Ianni, M.; Cama, A.; Veschi, S. Exploring the Immunomodulatory Potential of Pancreatic Cancer-Derived Extracellular Vesicles through Proteomic and Functional Analyses. Cancers2024, 16, 1795.
Piro, A.; Cufaro, M.C.; Lanuti, P.; Brocco, D.; De Lellis, L.; Florio, R.; Pilato, S.; Pagotto, S.; De Fabritiis, S.; Vespa, S.; Catitti, G.; Verginelli, F.; Simeone, P.; Pieragostino, D.; Del Boccio, P.; Fontana, A.; Grassadonia, A.; Di Ianni, M.; Cama, A.; Veschi, S. Exploring the Immunomodulatory Potential of Pancreatic Cancer-Derived Extracellular Vesicles through Proteomic and Functional Analyses. Cancers 2024, 16, 1795.
Abstract
Pancreatic cancer (PC) has a poor prognosis and displays resistance to immunotherapy. A better understanding of tumor-derived extracellular vesicles (EVs) 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. Proteomics of lymphocytes sorted from EV-treated, or -untreated PBMCs was performed and IFN-γ concentration was measured by ELISA. Notably, most of the proteins identified in Capan-2 and BxPC-3 EVs by proteomic analysis were connected in a single functional network (p=1x10-16) and were involved in “Immune System” (FDR: 1.10x10-24 and 3.69x10-19, respectively). Interestingly, 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. Proteomics of lymphocytes sorted from EV-treated PBMCs was consistent with their activation by Capan-2 EVs, indicating IFN-γ among major upstream regulators, as confirmed by ELISA. Proteomic and functional analyses indicate that PC-EVs have pleiotropic effects, and some may activate early immune response, which might be relevant for the development of highly needed immunotherapeutic strategies in this immune-cold tumor.
Biology and Life Sciences, Immunology and Microbiology
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