Identification of IFN-γ/IL-4 ratio as a new predictor and the significance of its based immune related prognostic model in diffuse large B-cell lymphoma

Background Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous malignant tumor of B-cell origin that is predisposed by abnormal immune function and is extremely challenging. Lymphocyte subsets and circulating cytokines are easily accessible immune indicators, which may be useful in prognostication of newly diagnosed DLBCL patients, independently. However, the association between these two clinical laboratory findings and prognostication of newly diagnosed DLBCL patients has not been studied. Method Here, we retrospectively analyzed 94 newly diagnosed DLBCL patients initially treated in our institution between 2017 and 2022. The prognostic influence of lymphocyte subsets, cytokines levels and other factors, including age, tumor stage on progression-free survival (PFS) and overall survival (OS) were studied by Kaplan–Meier curves as well as univariate and multivariate Cox regression models. Based on the findings in our center, we constructed an immune-related prognostic model and further validated it in an independent cohort from another center. Results The results suggested that IFN-γ/IL-4 ratio and CD4 + T cell count were independent risk variables for both PFS and OS in DLBCL patients. Besides, multivariate analysis showed that age was associated with the worse OS whereas CD8 + T cell count was associated with the inferior PFS. Moreover, elevated pretreatment IFN-γ/IL-4 ratio was significantly correlated with poor clinical response efficacy. Compared to patients experienced with death, lower level of IFN-γ/IL-4 ratio was discovered in surviving patients during the subsequent treatment cycles. Additionally, a new immune-related prognostic score model (IRPS) was constructed based on age, CD4 + T cell count and IFN-γ/IL-4 ratio, where high-risk patients had worse overall survival than low-risk patients. Meanwhile, the IRS could refine the IPI score well and validation of the IRS model in another independent cohort confirmed its effectiveness. Conclusion IFN-γ/IL-4 ratio is a simple, accessible but useful prognostic factor in newly diagnosed DLBCL patients, and the IRS model could better suggest PFS and OS of DLBCL, allowing for better risk stratification.