Crucial role of IL-6, IL-8, IL-11 and leptin in tumor microenvironment in a group of patients with GEP-NETs- crosstalk between inflammation and cancer.

Introduction: GEP-NETs constitute a heterogeneous group of rare cancers arising in biologically diverse microenvironments, while their cytokine profiles remain insufficiently characterized. Objectives: This study assessed IL-6, IL-8, IL-11 and leptin concentrations in tumor and corresponding surgical margins. Also, we aimed to determine the relationship between cytokines concentration and other clinical and demographic variables. Patients and methods: A multiplex immunoassay and ELISA were applied to quantify cytokine levels in tissue homogenates from 59 patients with GEP-NETs. Results: The significant differences between tumor and margin samples were identified, with higher concentrations of IL-6, IL-8, IL-11 and leptin in tumor. IL-6 and leptin levels were substantially elevated in tumors and margins from patients with T4. Tumor leptin levels were increased in patients with N2 vs. N0. Margin IL-11 concentration was higher in N0 compared with N2. Tumor IL-6 and leptin level was significantly higher in patients with M1 vs. M0. Moreover, cytokine levels varied according to tumor localization, with differences observed between pancreatic, ileal, colonic and small intestine tumors. Furthermore, IL-6, IL-8, and IL-11 were associated with comorbidities, IL-6 was associated with body mass, while altered leptin patterns appeared to reflect exposure to stimulants such as smoking. Conclusions: Our study demonstrated altered expression of IL-6, IL-8, IL-11, and leptin in GEP-NET tissues compared with corresponding surgical margins. The cytokines were associated with selected clinicopathological and socio-demographic variables. These findings support the relevance of inflammatory and metabolic signaling within the GEP-NET microenvironment and provide a basis for further studies investigating their potential biomarker value.