title: Immunosuppression in cervical cancer with special reference to arginase activity.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Group Infection and Cancer, School of Medicine and Corporación Académica para el Estudio de Patologías Tropicales, Universidad de Antioquia UdeA, Calle 70 No 52-21, Medellín, Colombia; School of Microbiology, Universidad de Antioquia UdeA, Calle 70 No 52-21, Medellín, Colombia.
authors.forename: Astrid M
authors.initials: AM
authors.lastname: Bedoya
authors.affiliation: Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA70112, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Tate
authors.affiliation: Group Infection and Cancer, School of Medicine and Corporación Académica para el Estudio de Patologías Tropicales, Universidad de Antioquia UdeA, Calle 70 No 52-21, Medellín, Colombia.
authors.forename: Armando
authors.initials: A
authors.lastname: Baena
authors.affiliation: Group Infection and Cancer, School of Medicine and Corporación Académica para el Estudio de Patologías Tropicales, Universidad de Antioquia UdeA, Calle 70 No 52-21, Medellín, Colombia; Hospital San Vicente Fundación, Calle 54 No 51D-154, Medellín, Colombia; Department of Gynecology and Obstetrics, School of Medicine, Universidad de Antioquia, UdeA, Calle 70 No 52-52, Medellin, Colombia.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Córdoba
authors.affiliation: Group Infection and Cancer, School of Medicine and Corporación Académica para el Estudio de Patologías Tropicales, Universidad de Antioquia UdeA, Calle 70 No 52-21, Medellín, Colombia; Department of Gynecology and Obstetrics, School of Medicine, Universidad de Antioquia, UdeA, Calle 70 No 52-52, Medellin, Colombia; Instituto de Cancerología Las Américas, Carrera 70 No 1-35, Torre 5, Medellín, Colombia.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Borrero
authors.affiliation: Instituto de Cancerología Las Américas, Carrera 70 No 1-35, Torre 5, Medellín, Colombia.
authors.forename: René
authors.initials: R
authors.lastname: Pareja
authors.affiliation: Instituto de Cancerología Las Américas, Carrera 70 No 1-35, Torre 5, Medellín, Colombia.
authors.forename: Fredy
authors.initials: F
authors.lastname: Rojas
authors.affiliation: Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA70112, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Patterson
authors.affiliation: Prevention and Intervention Group, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon CEDEX 08, France.
authors.forename: Rolando
authors.initials: R
authors.lastname: Herrero
authors.affiliation: Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA70112, USA. Electronic address: azea@lsuhsc.edu.
authors.forename: Arnold H
authors.initials: AH
authors.lastname: Zea
authors.affiliation: Group Infection and Cancer, School of Medicine and Corporación Académica para el Estudio de Patologías Tropicales, Universidad de Antioquia UdeA, Calle 70 No 52-21, Medellín, Colombia. Electronic address: sanchezg@medicina.udea.edu.co.
authors.forename: Gloria I
authors.initials: GI
authors.lastname: Sanchez
mesh_terms: D000328:Adult; D000368:Aged; D001119:Arginase / Q000378:metabolism*; D001120:Arginine / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000201:enzymology* / Q000276:immunology*; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D008875:Middle Aged; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000201:enzymology* / Q000276:immunology*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000097:blood / Q000201:enzymology* / Q000276:immunology*
chemical_list: D001120:Arginine; D001119:Arginase
keywords: Arginase activity and l-arginine; Cervical cancer; Colombia; Th2 cytokines