ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1656044
This article is part of the Research TopicCytokines and Chemokines in LymphomaView all articles
Elevated serum IL-10/IL-6 ratio as a novel biomarker for secondary central nervous system lymphoma and poor prognosis in DLBCL
Provisionally accepted
- Mianyang Central Hospital, Mianyang, China
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Diffuse large B-cell lymphoma (DLBCL), the most common non-Hodgkin lymphoma subtype, carries poor prognosis when systemic DLBCL involved in the central nervous system, which named secondary central nervous system lymphoma (SCNSL). While CNS-IPI predicts SCNSL risk, its limited sensitivity underscores the need for better biomarkers to improve risk stratification and enable early intervention.We compared pretreatment cytokines interleukin-10 (IL-10) and interleukin-6 (IL-6) in peripheral blood (PB) and cerebrospinal fluid (CSF), along with clinical characteristics, between patients with and without SCNSL.Results: Fifty-six newly diagnosed DLBCL patients who received more than two courses of treatment were included. Compared to patients without CNS relapse, SCNSL patients exhibited distinct clinical features including: higher frequency of B symptoms, increased bone marrow infiltration, and reduced B cell lymphoma 6 (BCL6) immunohistochemical positivity. Notably, SCNSL patients exhibited elevated serum IL-10 levels, increased serum IL-10/IL-6 ratios, higher CSF IL-10 concentrations, and greater CSF IL-10/IL-6 ratios. Multivariate analysis identified the elevated serum IL-10/IL-6 ratio (≥2.30) as an independent predictor for both progression-free survival (PFS) (HR=7.300, p=0.010) and SCNSL development (OR=43.200, p=0.001). There was no significant difference in time-to-CNS-relapse between high risk and non-high risk (low/intermediate risk) groups stratified by p=0.198). By incorporating the serum IL-10/IL-6 ratio into the CNS-IPI framework, we developed the CNS-IPI-ratio scoring system, with the high risk group showing significantly shorter median time-to-CNS-relapse than the non-high risk group (22.32 vs 40.35 months; χ²=5.680, p=0.017). While NCCN-IPI high risk and non-high risk groups showed comparable survival (p>0.05), integrating the serum IL-10/IL-6 ratio revealed significantly worse outcomes in high risk patients (PFS: p=0.046; OS: p=0.023). Additionally, SCNSL patients had significantly higher CSF IL-10/IL-6 ratios than those without SCNSL and controls (67.88 vs 0.74-0.79, p<0.05), and this ratio strongly correlated with CSF lactate dehydrogenase (LDH) (r=0.625, p=0.006).In DLBCL, an elevated serum IL-10/IL-6 ratio at diagnosis independently predicts DLBCL progression and the risk of SCNSL occurrence. The integration of the serum IL-10/IL-6 ratio significantly enhances the prognostic performance of both CNS-IPI and NCCN-IPI scoring systems. The CSF IL-10/IL-6 ratio represents a preliminary observation that suggests a potential trend toward diagnostic value for SCNSL identification.
Keywords: Diffuse large B-cell lymphoma, Central Nervous System, Interleukin-10, Interleukin-6, prognosis 1 Introduction
Received: 29 Jun 2025; Accepted: 18 Jul 2025.
Copyright: © 2025 Wen, Nie, Zhou, Liu, Yue, Zhang, Su, Liang and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Fang Xu, Mianyang Central Hospital, Mianyang, China
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