Plasma IL-35 in Mature T-Cell Neoplasms: An Exploratory Single-Centre Study

INTRODUCTION: Mature T-cell neoplasms are biologically heterogeneous diseases with generally poor outcomes, and circulating immunoregulatory cytokines may reflect clinically relevant tumor immune interactions. This exploratory study evaluated plasma IL-35, IL-10, and IL-2 at diagnosis and examined their relationship with overall survival. METHODS: Twenty patients with histologically confirmed mature T-cell neoplasms and available diagnostic EDTA plasma were included. Plasma IL-35 was measured by ELISA. Because multiple numerical estimates were below the validated quantitative range, survival analyses used the manufacturer's analytical sensitivity (9.38 pg/mL) as the primary assay based threshold and 15.63 pg/mL, the lower boundary of the validated quantitative range, as a sensitivity threshold. Overall survival was analyzed using Kaplan-Meier/log-rank methods and univariable Cox regression. A disease-scope sensitivity analysis excluded the two primary cutaneous T-cell neoplasms. RESULTS: Plasma IL-35 showed marked interpatient heterogeneity. Because several numerical estimates were below the validated quantitative range of the assay, survival analyses categorized IL-35 according to assay-defined analytical thresholds rather than treating low values as precise continuous measurements. Using the manufacturer's analytical sensitivity (9.38 pg/mL), patients with IL-35 ≥9.38 pg/mL had longer OS than those below this threshold (log-rank p = 0.029; HR 0.26, 95% CI 0.07-0.99; p = 0.049). The association was consistent using 15.63 pg/mL, the lower boundary of the validated quantitative assay range (log-rank p = 0.012; HR 0.12, 95% CI 0.015-0.92; p = 0.041). A sensitivity analysis restricted to the 18 patients with systemic disease showed the same direction of association. IL-2 and IL-10 were quantifiable in only three patients each and were considered descriptive. CONCLUSION: Higher plasma IL-35 relative to assay defined analytical thresholds was associated with longer OS in this exploratory cohort. The association remained evident in sensitivity analyses using the lower boundary of the validated assay range and after exclusion of the two primary cutaneous T-cell neoplasms. Given the small and histologically heterogeneous cohort and the limited number of events, these findings should be considered hypothesis-generating and require validation in larger, disease-specific prospective cohorts.