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

Anna Piro; Maria Concetta Cufaro; Paola Lanuti; Davide Brocco; Laura De Lellis; Rosalba Florio; Serena Pilato; Sara Pagotto; Simone De Fabritiis; Simone Vespa; Giulia Catitti; Fabio Verginelli; Pasquale Simeone; Damiana Pieragostino; Piero Del Boccio; Antonella Fontana; Antonino Grassadonia; Alessandro Cama; Serena Veschi

doi:10.20944/preprints202404.0909.v1

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preprints.org > biology and life sciences > immunology and microbiology > doi: 10.20944/preprints202404.0909.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Anna Piro

Maria Concetta Cufaro

^* ,

Version 1 : Received: 11 April 2024 / Approved: 15 April 2024 / Online: 15 April 2024 (07:21:04 CEST)

How to cite: 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.; Cama, A.; Veschi, S. Exploring the Immunomodulatory Potential of Pancreatic Cancer-Derived Extracellular Vesicles through Proteomic and Functional Analyses. Preprints 2024, 2024040909. https://doi.org/10.20944/preprints202404.0909.v1 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.; Cama, A.; Veschi, S. Exploring the Immunomodulatory Potential of Pancreatic Cancer-Derived Extracellular Vesicles through Proteomic and Functional Analyses. Preprints 2024, 2024040909. https://doi.org/10.20944/preprints202404.0909.v1

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MDPI and ACS Style

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.; Cama, A.; Veschi, S. Exploring the Immunomodulatory Potential of Pancreatic Cancer-Derived Extracellular Vesicles through Proteomic and Functional Analyses. Preprints 2024, 2024040909. https://doi.org/10.20944/preprints202404.0909.v1

APA Style

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., Cama, A., & Veschi, S. (2024). Exploring the Immunomodulatory Potential of Pancreatic Cancer-Derived Extracellular Vesicles through Proteomic and Functional Analyses. Preprints. https://doi.org/10.20944/preprints202404.0909.v1

Chicago/Turabian Style

Piro, A., Alessandro Cama and Serena Veschi. 2024 "Exploring the Immunomodulatory Potential of Pancreatic Cancer-Derived Extracellular Vesicles through Proteomic and Functional Analyses" Preprints. https://doi.org/10.20944/preprints202404.0909.v1

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.

Keywords

pancreatic cancer; extracellular vesicles; immune response

Subject

Biology and Life Sciences, Immunology and Microbiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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