High serum levels of B‐lymphocyte stimulator are associated with clinical–pathological features and outcome in classical Hodgkin lymphoma

Abstract

SummaryB‐lymphocyte stimulator (BLyS) acts as survival factor for B lymphocytes. As Hodgkin and Reed‐Sternberg (HRS) cells express receptors through which BLyS promotes their growth and chemotherapy resistance, we investgated whether this molecule was increased in sera from patients with classical Hodgkin lymphoma (cHL) and whether it correlates with clinical‐pathological features and outcomes. Enzyme‐linked immunosorbent assay was used to measure soluble BLyS (sBLyS) in sera from 87 patients and 33 donors; higher levels were detected in patients (mean ± standard error 4493·9 ± 264·9 pg/ml vs. 2687·0 ± 200·9 pg/ml; P < 0·0001). Levels above the median value (4242·0 pg/ml) were associated with age ≥45 years (P = 0·042), advanced stages of disease (P = 0·005), systemic symptoms (P = 0·014) and extranodal involvement (P = 0·009). Five‐year failure‐free survival (FFS) of patients with sBLyS below or equal to median levels was 88·6% as compared to 65·1% of those with levels above the median (P = 0·009). Statistical analyses confirmed the prognostic significance of sBLyS (P = 0·046). When patients were analysed according to variables associated with high levels, sBLyS showed an independent predictive power in terms of FFS. Our findings support the involvement of BLyS in cHL pathogenesis. The association between high serum levels and an inferior FFS indicates that sBLyS is a possible prognostic predictor with a potential significance as a therapeutic target.

Functional coexpression of Interleukin (IL)‐7 and its receptor (IL‐7R) on Hodgkin and Reed‐Sternberg cells: Involvement of IL‐7 in tumor cell growth and microenvironmental interactions of Hodgkin's lymphoma

“…60 As opposed to carcinomas, the presence of a high proportion of Tregs in tumor tissues has been correlated with a favorable prognosis in patients with HL, 56 further highlighting important differences in the microenvironmental regulation of tumor cells between HL and other malignancies. 18,19 As Tregs express both CCR5 and CCR4 receptors, it is tempting to speculate that H-RS cells might first recruit cells by means of TARC/CCL17 and MDC/CCL22 or Rantes/CCL5 4,61-63 and then sustain their growth and/or survival through tumor-derived cytokines including IL-7. The relative proportion of Foxp31 cells in HL tissues changes during the course of the disease being lower at presentation and at relapse.…”

“…15,16 The abnormal systemic levels of some of these cytokines and/or chemokines have been shown to represent unfavorable prognostic factors affecting the clinical outcome. [17][18][19][20] A further hallmark of the ''pseudo'' inflammatory milieu of HL is the expansion of CD41 CD251 FOXP31 CD127 low T-cells (Tregs). Increasing evidence indicates that H-RS cells are able to recruit and/or induce Tregs that negatively regulate immune response to self or nonself antigens and may contribute to the ineffective immune clearance of the malignant cells.…”

High APRIL but not BAFF serum levels are associated with poor outcome in patients with follicular lymphoma

“…Several studies have shown that BAFF may promote in vitro malignant B cell growth and survival by upregulating antiapoptotic proteins, such as Bcl-2 and Bcl-xL, and downregulating proapoptotic proteins, such as Bax [11,21]. Moreover, high BAFF serum levels have been reported to be significantly associated with poor survival outcomes for DLBCL, HL, and CLL [15,18,19,28]. Thus, we hypothesized that elevated BAFF serum levels predispose patients to increased FL cell growth and subsequently shorter PFS and OS.…”

“…Elevated BAFF and APRIL serum levels have been found in a number of hematopoietic and lymphoid malignancies including B cell chronic lymphocytic leukemia (B-CLL), FL, DLBCL, Hodgkin's lymphoma (HL), and multiple myeloma (MM) [15][16][17][18][19][20][21]. It has also been suggested that the elevated BAFF and APRIL serum levels in patients with HL and B lymphocyte malignancies may have prognostic value [15][16][17][18][19].…”

“…It has also been suggested that the elevated BAFF and APRIL serum levels in patients with HL and B lymphocyte malignancies may have prognostic value [15][16][17][18][19]. Although numerous advances have been made in our understanding of the role of this ligand/receptor system in lymphomas, the prognostic significance of BAFF and APRIL serum levels in FL remains unknown.…”