The prognostic value of the myeloid-mediated immunosuppression marker Arginase-1 in classic Hodgkin Lymphoma

Alessandra Romano, Nunziatina Laura Parrinello, Calogero Vetro, Daniele Tibullo, Cesarina Giallongo, Piera La Cava, Annalisa Chiarenza, Giovanna Motta, Anastasia L. Caruso, Loredana Villari, Claudio Tripodo, Sebastiano Cosentino, Massimo Ippolito, Ugo Consoli, Andrea Gallamini, Stefano Pileri, Francesco Di Raimondo

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)67333-67346
Number of pages14
JournalOncotarget
Volume7
Issue number41
DOIs
Publication statusPublished - 2016

Keywords

  • Arginase-1
  • Hodgkin Lymphoma
  • PET-2

ASJC Scopus subject areas

  • Oncology

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