title: The prognostic value of the myeloid-mediated immunosuppression marker Arginase-1 in classic Hodgkin lymphoma.
abstract: Neutrophilia is hallmark of classic Hodgkin Lymphoma (cHL), but its precise characterization remains elusive. We aimed at investigating the immunosuppressive role of high-density neutrophils in HL.
  
  
  
  First, N-HL function was evaluated in vitro, showing increased arginase (Arg-1) expression and activity compared to healthy subjects. Second, we measured serum level of Arg-1 (s-Arg-1) by ELISA in two independent, training (N = 40) and validation (N = 78) sets.
  
  
  
  s-Arg-1 was higher in patients with advanced stage (p = 0.045), B-symptoms (p = 0.0048) and a positive FDG-PET scan after two cycles of chemotherapy (PET-2, p = 0.012). Baseline levels of s-Arg-1 > 200 ng/mL resulted in 92% sensitivity and 56% specificity to predict a positive PET-2.Patients showing s-Arg-1 levels > 200 ng/mL had a shorter progression free survival (PFS). In multivariate analysis, PET-2 and s-Arg-1 at diagnosis were the only statistically significant prognostic variables related to PFS (respectively p = 0.0004 and p = 0.012).Moving from PET-2 status and s-Arg-1 level we constructed a prognostic score to predict long-term treatment outcome: low s-Arg-1 and negative PET-2 scan (score 0, N = 63), with a 3-Y PFS of 89.5%; either positive PET-2 or high s-Arg-1 (score 1, N = 46) with 3-Y PFS of 67.6%, and both positive markers (score 2, N = 9) with a 3-Y PFS of 37% (p = 0.0004).
  
  
  
  We conclude that N-HL are immunosuppressive through increased Arg-1 expression, a novel potential biomarker for HL prognosis.
authors.affiliation: Division of Hematology, AOU "Policlinico - Vittorio Emanuele", University of Catania, Catania, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Romano
authors.affiliation: Division of Hematology, AOU "Policlinico - Vittorio Emanuele", University of Catania, Catania, Italy.
authors.forename: Nunziatina Laura
authors.initials: NL
authors.lastname: Parrinello
authors.affiliation: Division of Hematology, AOU "Policlinico - Vittorio Emanuele", University of Catania, Catania, Italy.
authors.forename: Calogero
authors.initials: C
authors.lastname: Vetro
authors.affiliation: Division of Hematology, AOU "Policlinico - Vittorio Emanuele", University of Catania, Catania, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Tibullo
authors.affiliation: Division of Hematology, AOU "Policlinico - Vittorio Emanuele", University of Catania, Catania, Italy.
authors.forename: Cesarina
authors.initials: C
authors.lastname: Giallongo
authors.affiliation: Division of Hematology, AOU "Policlinico - Vittorio Emanuele", University of Catania, Catania, Italy.
authors.forename: Piera
authors.initials: P
authors.lastname: La Cava
authors.affiliation: Division of Hematology, AOU "Policlinico - Vittorio Emanuele", University of Catania, Catania, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiarenza
authors.affiliation: Division of Hematology, AOU "Policlinico - Vittorio Emanuele", University of Catania, Catania, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Motta
authors.affiliation: Division of Hematology, AOU "Policlinico - Vittorio Emanuele", University of Catania, Catania, Italy.
authors.forename: Anastasia L
authors.initials: AL
authors.lastname: Caruso
authors.affiliation: Division of Pathology, AOU "Policlinico - Vittorio Emanuele", Catania, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Villari
authors.affiliation: Tumor Immunology Unit, Department of Health Science, University of Palermo, Palermo, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Tripodo
authors.affiliation: Nuclear Medicine Center, Azienda Ospedaliera Cannizzaro, Catania, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Cosentino
authors.affiliation: Nuclear Medicine Center, Azienda Ospedaliera Cannizzaro, Catania, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Ippolito
authors.affiliation: Division of Hematology, ARNAS Garibaldi, Catania, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: Consoli
authors.affiliation: Research, Innovation and Statistics Department. A. Lacassagne Cancer Centre, Nice, France.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gallamini
authors.affiliation: Unità di Diagnosi Emolinfopatologica, IEO, Milano, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Pileri
authors.affiliation: Division of Hematology, AOU "Policlinico - Vittorio Emanuele", University of Catania, Catania, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Raimondo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001119:Arginase / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000201:enzymology* / Q000276:immunology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D011379:Prognosis; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C574619:ARG1 protein, human; D001119:Arginase
keywords: Arginase-1; PET-2; Hodgkin lymphoma