Cytokine concentrations in pediatric primary mediastinal large B cell lymphoma correlate with disease extent and outcome

Primary mediastinal large B-cell lymphoma (PMBCL) predominantly affects female adolescents and young adults. It displays an immune-privileged phenotype and demonstrates the involvement of key cytokine signaling pathways, including increased expression of Thymus and activation-regulated chemokine (TARC/CCL17). Currently, there is a lack of established markers for stratification. We studied plasma concentrations of 24 cytokines at diagnosis in a large population-based pediatric cohort of 62 patients with PMBCL. Compared to a group of age-matched patients with other types of lymphoma in long-term remission and healthy individuals (n=26), we detected elevated concentrations of CCL4, CCL17, interleukin (IL)-6, CXCL8, CXCL9, CXCL10, and CXCL11. The median CCL17 level was 1695 pg/ml (IQR, 642-3142) in patients with PMBCL compared to 81 pg/ml (IQR, 41-190) in controls (p < 0.0001). Concentrations of CCL17, CXCL9, and CXCL10 significantly correlated with mediastinal tumor volume (MTV) and lactate dehydrogenase activity (LDH) but were not associated with event-free survival (EFS). Concentrations of IL-17F and IL-22 were inversely correlated with LDH and MTV. Elevated IL-6, IL-10, IL-17A, and IL-22 were significantly correlated with inferior EFS in a subgroup of 50 patients uniformly treated with dose-adjusted EPOCH with rituximab. Although based on a limited number of events, IL-6 showed the strongest association with outcome (hazard ratio of 6.8 (95%-CI, 1.5-30.9). In summary, pretreatment cytokine levels in patients with PMBCL reveal distinct patterns associated with tumor burden (CCL17, CXCL9, CXCL10) and outcome (IL-6, IL-10, IL-17A, IL-22).