{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:28:10Z","timestamp":1791041290704,"version":"4.1.0"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and carries a poor prognosis when it involves the central nervous system (CNS), a condition known as secondary CNS lymphoma (SCNSL). Although the CNS International Prognostic Index (CNS-IPI) is used to estimate SCNSL risk, its limited sensitivity highlights the need for more reliable biomarkers to improve risk stratification and enable earlier intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We evaluated pretreatment levels of interleukin-10 (IL-10) and interleukin-6 (IL-6) in both peripheral blood (PB) and cerebrospinal fluid (CSF), and compared clinical characteristics between DLBCL patients with and without SCNSL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifty-six newly diagnosed DLBCL patients who received at least two treatment cycles were included. Compared to patients without CNS relapse, those with SCNSL exhibited distinct clinical features: more frequent B symptoms, increased bone marrow involvement, and lower B-cell lymphoma 6 (BCL6) immunohistochemical positivity. Biochemically, SCNSL patients showed elevated serum IL-10 levels, higher serum IL-10\/IL-6 ratios, increased CSF IL-10 concentrations, and markedly elevated CSF IL-10\/IL-6 ratios. On multivariate analysis, a serum IL-10\/IL-6 ratio \u22652.30 independently predicted both progression-free survival (PFS) (HR = 7.300,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.010) and SCNSL development (OR = 43.200,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.001). Notably, time to CNS relapse did not significantly differ between high- and non-high-risk groups defined by CNS-IPI (\u03c7\u00b2 = 1.654,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.198). However, incorporating the serum IL-10\/IL-6 ratio into the CNS-IPI yielded a refined scoring model\u2014CNS-IPI-ratio\u2014where the high-risk group had a significantly shorter median time to CNS relapse compared to the non-high-risk group (22.32 vs. 40.35 months; \u03c7\u00b2 = 5.680,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.017). Although survival outcomes were similar between high- and non-high-risk groups based on the NCCN-IPI alone (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;gt; 0.05), adding the serum IL-10\/IL-6 ratio identified significantly poorer outcomes in high-risk patients (PFS:\n                      <jats:italic>p<\/jats:italic>\n                      = 0.046; OS:\n                      <jats:italic>p<\/jats:italic>\n                      = 0.023). Furthermore, SCNSL patients demonstrated significantly higher CSF IL-10\/IL-6 ratios compared to non-SCNSL patients and controls (67.88 vs. 0.74\u20130.79,\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05), with this ratio strongly correlating with CSF lactate dehydrogenase (LDH) levels (r = 0.625,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.006).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In DLBCL, an elevated serum IL-10\/IL-6 ratio at diagnosis independently predicts disease progression and SCNSL risk. Incorporating this biomarker enhances the prognostic utility of both CNS-IPI and NCCN-IPI models. Additionally, the markedly elevated CSF IL-10\/IL-6 ratio in SCNSL patients suggests potential diagnostic value for CNS involvement, warranting further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1656044","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T06:33:29Z","timestamp":1755066809000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Elevated serum IL-10\/IL-6 ratio as a novel biomarker for secondary central nervous system lymphoma and poor prognosis in 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