Stage-resolved cytokine profiling nominates IL-17 as a prognostic node in relapsed/refractory B-cell lymphoma.

BACKGROUND: B-cell non-Hodgkin lymphoma (B-NHL) and B-cell acute lymphoblastic leukemia (B-ALL) are highly heterogeneous malignancies. While immunochemotherapy and CD19 chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of newly diagnosed (ND) and relapsed or refractory (R/R) disease, clinical outcomes remain inconsistent. This study aims to evaluate a baseline levels of 12-cytokine panel across the ND, R/R, and CAR-T cohorts to identify robust biomarkers predictive of treatment response and long-term prognosis. METHODS: We enrolled 120 patients (ND B-NHL: n = 42; R/R B-NHL: n = 52; ND B-ALL: n = 10; R/R B-ALL: n = 21) and a separate cohort of 23 patients receiving CD19 CAR-T therapy. Plasma levels of 12 cytokines were quantified and analyzed using ROC curves, Kaplan-Meier survival analysis, and regression analyses to determine independent prognostic factors. RESULTS: Baseline cytokine profiling revealed that IL-17 was one of the four markers exhibiting significant inter-group differences (P = 0.034). In the R/R B-NHL cohort, high baseline IL-17 was significantly associated with inferior OS (log-rank P < 0.0001) and shorter progression-free survival (PFS) (P = 0.003). Univariate and multivariate Cox regression confirmed IL-17 as a significant risk factor for poor OS (HR = 1.802, P < 0.001) and PFS (HR = 1.279, P = 0.048) in R/R B-NHL. In CAR-T cohort, IL-17 levels also provided substantial discrimination for PFS (AUC 0.725). CONCLUSION: Our findings indicate that IL-17 may be a potential biomarker with stage-specific clinical associations in B-NHL. Its relevance may vary across disease stages, but overall, it warrants further investigation for risk stratification and individualized treatment monitoring.