The prognostic value of the myeloid-mediated immunosuppression marker Arginase-1 in classic Hodgkin lymphoma
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Alessandra Romano1, Nunziatina Laura Parrinello1, Calogero Vetro1, Daniele Tibullo1, Cesarina Giallongo1, Piera La Cava1, Annalisa Chiarenza1, Giovanna Motta1, Anastasia L. Caruso1, Loredana Villari2, Claudio Tripodo3, Sebastiano Cosentino4, Massimo Ippolito4, Ugo Consoli5, Andrea Gallamini6, Stefano Pileri7, Francesco Di Raimondo1
1Division of Hematology, AOU “Policlinico - Vittorio Emanuele”, University of Catania, Catania, Italy
2Division of Pathology, AOU “Policlinico - Vittorio Emanuele”, Catania, Italy
3Tumor Immunology Unit, Department of Health Science, University of Palermo, Palermo, Italy
4Nuclear Medicine Center, Azienda Ospedaliera Cannizzaro, Catania, Italy
5Division of Hematology, ARNAS Garibaldi, Catania, Italy
6Research, Innovation and Statistics Department. A. Lacassagne Cancer Centre, Nice, France
7Unità di Diagnosi Emolinfopatologica, IEO, Milano, Italy
Alessandra Romano, email: [email protected]
Francesco Di Raimondo, email: [email protected]
Keywords: Arginase-1, Hodgkin lymphoma, PET-2
Received: June 30, 2016 Accepted: September 05, 2016 Published: September 14, 2016
Purpose: 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.
Experimental design: 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.
Results: 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).
Conclusions: We conclude that N-HL are immunosuppressive through increased Arg-1 expression, a novel potential biomarker for HL prognosis.
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