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2016 ; 7
(41
): 67333-67346
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The prognostic value of the myeloid-mediated immunosuppression marker Arginase-1
in classic Hodgkin lymphoma
#MMPMID27637084
Romano A
; Parrinello NL
; Vetro C
; Tibullo D
; Giallongo C
; La Cava P
; Chiarenza A
; Motta G
; Caruso AL
; Villari L
; Tripodo C
; Cosentino S
; Ippolito M
; Consoli U
; Gallamini A
; Pileri S
; Di Raimondo F
Oncotarget
2016[Oct]; 7
(41
): 67333-67346
PMID27637084
show ga
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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