Chemokine Receptor Profiles as Predictors of Survival and Early Progression in Follicular Lymphoma

Objective: Classical follicular lymphoma (FL) is a heterogeneous malignancy. Early progression within 24 months (POD24) is linked to poor outcomes. However, precise risk stratification remains unclear. We aimed to explore chemokine receptor (CR) expression profiles as potential markers of disease biology and outcome in FL. Methods: We analyzed mRNA expression of CCR1-CCR10, CXCR1-CXCR5, CX3CR1, and XCR1 in 52 FL samples (13 POD24, 39 non-POD24) using RT-qPCR. Immunohistochemistry for CCR3, CCR7, CXCR3, CXCR4, and CXCR5 was performed. Reactive tonsils (n = 5) served as controls. Results: Compared to controls, FL samples showed lower CCR1, CCR6, CCR7, CXCR1, CXCR5, and CX3CR1 but higher CCR4, CCR5, CCR8, and CCR9 expression. Grade 3a FL correlated with reduced CCR8, CXCR1, and CXCR3, and increased CCR7. POD24 cases had elevated CCR3, CCR4, CCR7, CXCR4, and XCR1 but reduced CXCR3. High CCR3, CCR4, and CCR10 levels were linked to inferior survival. Cluster analysis revealed two CR-based subgroups; most POD24 cases clustered in the group with worse prognosis. Conclusion: These findings suggest distinct chemokine receptor expression profiles contribute to FL progression. Our data highlight several CRs as candidate prognostic markers and potential therapeutic targets in the context of POD24, warranting further investigation in larger, prospective cohorts. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.