High number of CD14+B7H4+ monocytes is significantly associated with increased concentrations of IL-4, IL-13, IL-10, and TGF-β1 in tumor microcirculation of lung carcinoma

Abstract

Introduction. Lung cancer is one of leading causes of mortality. Disease progression and advanced disease are characterized with unprotective immune response due to M2 macrophage polarization, MDSC activity, cytokine imbalance and regulatory T lymphocyte activity. Material and methods. We have investigated principal Th1/Th2 cytokines and CD14 + B7H4 + monocyte number in blood and tumor microcirculation samples of 41 lung cancer patients (III and IV clinical stage) and 30 controls. Aim. To investigate association between Th1/Th2 cytokines and CD14 + B7H4 + monocyte number in LC patients. Results. Concentration of investigated cytokines in all patients vs heathy controls did not differ significantly. Stratification in groups according to tumor histology, disease extent and tumor size revealed significant differences. LC patients with different histology type demonstrated significant differences, both in serum and microcirculation samples. Presence of metastasis was associated with increased IFN-g/IL-4 in blood and increased IL-13 in tumor microcirculation samples. Tumor microcirculation samples of the largest tumors was characterized with Th2 cytokine profile. Investigation of CD14 + B7H4 + Mo in blood samples demonstrated significant association of extreme value of this cell population with elevated IL-2/IL-13. Patients with the highest CD14 + B7H4 + number in tumor microcirculation samples demonstrated significant increment of IL-4, IL-13, IL-10, and TGF-1. Conclusion.LC patients demonstrated polarization of cytokine response associated with microenvironment origin, tumor histology type, tumor size and disease extent. The highest number of CD14 + B7H4 + monocytes is significantly associated with Th2 cytokine profile.

A systematic review and meta-analysis to evaluate blood levels of interleukin-6 in lung cancer patients

“…Out of all the articles included in the meta-analysis [27][28][29][30][31], only one study [27] reported a significantly lower level of IL-6, while 20 studies [28, 29, 39, 45-52, 54, 55, 58-62, 65, 66] found a higher level of IL-6 in LC cases than in HCs. The remaining studies [30,31,53,56,57,64] did not find any significant difference between the two groups. Some studies [57,58,67] showed that serum IL-6 was linked to anxiety and depression in LC cases.…”

“…Twenty-eight studies [27][28][29][30][31] were published from 1996 to 2022 (Table I). Among all studies, eleven studies were reported in Caucasians, fourteen in Asians, and three in mixed ethnicities.…”

“…Various articles have reported on the serum/plasma levels of IL-6 in LC patients compared to healthy controls (HCs), yielding different results [27][28][29][30][31]. To our knowledge,…”