Assessment and Prognostic Significance of a Serum Cytokine Panel in Diffuse Large B-cell Lymphoma

Abstract Objective To assess the contents of circulating cytokines in patients with diffuse large B-cell lymphoma (DLBCL), and to examine their relationship with clinicopathological manifestations and prognosis. Method We recruited 72 DLBCL patients, 11 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) patients, and 56 healthy controls from our hospital between the period of January 2017 and January 2020, and measured 7 serum cytokine contents using Beckman Navios flow cytometry. The cytokine level was compared between DLBCL patients and healthy controls using one way ANOVA. Two-sided Spearman test was employed for relationship evaluation between circulating cytokine levels and clinicopathological characteristics, IPI score, and short-term treatment response within DLBCL patients. The inter-group comparison of cytokine levels employed the Mann Whitney test. The support vector machine (SVM) was utilized for the cytokine evaluation-based prediction of DLBCL patient short-term treatment response. Lastly, survival curves were used to assess correlation between the aforementioned cytokines and overall survival. Result The IL-6, IL-10, and IFN-γcontents were markedly enhanced among DLBCL patients, as opposed to healthy controls ( P < 0.05). Patients with enhanced circulating LDH expressed elevated IL-10 level (P < 0.05), and patients with augmented CRP expressed upregulated IL-6 and IL-10 levels, and the rise in IL-6 levels was positively associated with serum CRP ( P = 0.00, r = 0.66). Additionally, the international prognostic index (IPI) risk stratification of DLBCL patients was strongly associated with the circulating IL-6 and IL-10 contents. Enhanced IL-6, IL-10, and TNF-α levels often produced worse short-term treatment efficacies ( P < 0.05). Moreover, the accuracy of short-term treatment response prediction model of DLBCL patients, obtained using SVM, was 81.63%. Using long-term follow-up, we further revealed that the DLBCL patients who expired within one year exhibited enhanced circulating IL-6 and IL-10 levels, compared to patients who survived, however, the IL-17 level was drastically reduced ( P < 0.05). Despite the aforementioned evidences, we observed no marked association between the specified cytokines and overall survival (OS). Conclusion The IL-6, IL-10, IL-17, TNF-α, and IFN-γ contents can potentially serve as biological indicators of DLBCL tumor immune status, and a combined application with the IPI score can be a robust indicator for DLBCL patient prognosis. Our findings provide novel ideas for the clinical treatment of DLBCL patients.