Characterization of the perioperative changes of exosomal immune-related cytokines induced by prostatectomy in early-stage prostate cancer patients

• Published in: Cytokine (Philadelphia, Pa.) Vol. 141; p. 155471
• Main Authors: Macías, Mónica, García-Cortés, Ángel, Torres, Marcos, Ancizu-Marckert, Javier, Ignacio Pascual, Juan, Díez-Caballero, Fernando, Enrique Robles, José, Rosell, David, Miñana, Bernardino, Mateos, Beatriz, Ajona, Daniel, Sánchez-Bayona, Rodrigo, Bedialauneta, Oihane, Chocarro, Susana, Navarro, Ana, Andueza, María P., Gúrpide, Alfonso, Perez-Gracia, Jose Luis, Alegre, Estibaliz, González, Álvaro
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-05-2021
• Subjects: Adult; Aged; Cancer; Chemokines - immunology; Cytokines; Exosomes; Exosomes - immunology; Humans; Male; Middle Aged; Myeloid-derived suppressor cells; Myeloid-Derived Suppressor Cells - immunology; Neoplasm Proteins - immunology; Neoplasm Staging; Perioperative Period; Prostate; Prostatectomy; Prostatic Neoplasms - immunology; Prostatic Neoplasms - pathology; Prostatic Neoplasms - surgery; Tumor Microenvironment - immunology; MDSCs; Cytokines; Myeloid-derived suppressor cells; MIF; Exosomes; Prostate; PCa; PSA; Cancer
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2021.155471

•We analyzed MDSCs cytokines in serum exosomes from prostate cancer patients.•CCL2, CXCL2, CXCL5, CXCL8, MIF, S100A9 and TGF-ß were detected in exosomes.•MIF, TGF-ß and CXCL2 were enriched in exosomes in relation to other cytokines.•Prostate cancer exosomes had increased CCL2, CXCL5 levels compared to control.•Radical prostatectomy decreased CCL2, CXCL5 exosome levels.
Myeloid-derived suppressor cells (MDSCs) are relevant in prostate cancer microenvironment collaborating in tumor development. The main tumor marker used in this disease, prostate-specific antigen (PSA), does not provide information related to this tumor microenvironment. Cancer cells secrete exosomes carrying bioactive molecules contributing to MDSCs recruitment and induction. The aim of this study was to characterize the perioperative changes of exosomal cytokines relevant in MDSCs recruitment induced by prostatectomy in prostate cancer patients.
Blood was drawn from 26 early-stage prostate cancer patients before and after radical prostatectomy and from 16 healthy volunteers. Serum exosomes were separated by precipitation. Cytokines related with MDSC cell recruitment and activation CCL2, CXCL2, CXCL5, CXCL8, CXCL12, MIF, S100A9 and TGF-ß were measured in serum and serum-derived exosomes using immunometric assays.
All cytokines were detected both in serum and exosomes, except for CXCL12, which was detected only in serum. Exosomes were enriched specially in MIF, TGF-ß and CXCL2. Presurgical MIF levels in exosomes correlated negatively with serum PSA. Also, presurgical TGF-ß decreased both in serum and exosomes as Gleason score rises. Patientś presurgical exosomes had increased CCL2, CXCL5 and TGF-ß levels than exosomes from healthy controls. These differences were not observed when cytokines were analyzed in serum, except for TGF-ß. Cytokine levels of CCL2, CXCL5 decreased in patients’ postsurgical exosomes, while TGF-ß further increased. On the contrary, S100A9 levels were lower in patientś presurgical exosomes but increased after radical prostatectomy.
Blood exosomal content in cytokines constitute an attractive source to evaluate MDSCs immunomodulators providing additional information related to tumor microenvironment in prostate cancer.