Immunosuppression in Cervical Cancer with Special Reference to Arginase Activity

ABSTRACT: Introduction: Cervical cancer is characterized by an immunosuppressive microenvironment and a Th2-type cytokine profile. Expression of arginase (ASE), the enzyme that converts L-arginine into L-ornithine and urea, is stimulated by Th2-type cytokines. Objective: To assess the association of ASE activity and L-Arg metabolism products with cervical cancer. Methods: Sera of 87 and 41 women with histologically confirmed by colposcopy-directed biopsy SCC and CIN3 respectively and 79 with normal cytology or Low-Grade Squamous Intraepithelial Lesion (LSIL), were evaluated. Cytokines were measured using Milliplex Human cytokine/chemokine kit. Arginase (ASE) activity was determined using an enzymatic assay. Levels of L-arginine, L ornithine, putrescine and spermine were determined by HPLC. Results: Significantly higher levels of ASE activity were observed in women with CIN3 (age-adjusted OR: 24.3; 95%CI: 3.82–155) and SCC (AOR: 9.8; 95%CI: 2.34–40.8). As expected, possibly due to high levels of ASE activity, higher levels of L-Arg were negatively associated with CIN3 (AOR: 0.03; 95%CI: 0.004–0.19) and SSC (AOR: 0.06; 95%CI: 0.02–0.24). Consistent with the role of ASE in the conversion of L-arginine to L-ornithine and polyamine production therefrom, women with cervical cancer had higher levels of spermine and putrescine. A correlation analysis revealed a significant albeit weak relationship between high levels of IL-10 and high levels of ASE (Pearson r = 0.32, p-value = 0.003) in women with cervical cancer. Conclusion: This study indicates that ASE activity and L-Arg degradation mechanisms of immunosuppression are present in cervical cancer. The results foster research in the design of possible strategies to inhibit ASE activity for therapy of cervical cancer.

• Autores: Bedoya, Astrid Milena; Tate, David; Baena Zapata, Armando; Córdoba Gómez, Carlos Mario; Borrero Franco, Mauricio; Pareja, René; Rojas, Fredy; Patterson, John; Herrero, Rolando; Zea, Arnold; Sánchez Vásquez, Gloria
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2014
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/32451
• Acceso en línea: https://hdl.handle.net/10495/32451; https://www.sciencedirect.com/science/article/pii/S0090825814012190?via%3Dihub
• Palabra clave: Uterine Cervical Neoplasms; Neoplasias del Cuello Uterino; Arginase; Arginasa; Arginine; Arginina; Cytokines; Citocinas; Th1-Th2 Balance; Balance Th1 - Th2; Colombia
• Rights: openAccess
• License: http://creativecommons.org/licenses/by-nc-nd/2.5/co/