COMPARATIVE ANALYSIS OF CYTOKINE PRODUCTION BY BLOOD IMMUNOCOMPETENT CELLS AND TUMOR IN DIFFERENT AGE GROUPS OF PATIENTS WITH INVASIVE DUCTAL CARCINOMA

Abstract

It is known that a relationship exists between patient’s age and pathogenesis of malignant tumors associated with ability of tumor and its microenvironment to secrete cytokines that may play an important role in carcinogenesis. The aim of present study was a comparative analysis of cytokine production by peripheral blood cells and tumor samples when exposed to polyclonal activators (PA) in patients of different age groups with invasive ductal carcinoma. Peripheral blood samples of 54 women with invasive ductal carcinoma were under study. The patients were divided into the following groups: I, 40-60 years old; II, 61 year and older. Metastases into lymph nodes were revealed at the moment of study in 13 patients (42%) from group I. By contrast, only 3 of 23 (10%) patients with metastases were revealed in group II. Fisher’s ratio test showed significant differences between occurrence of metastases in lymph nodes, and patient age (p = 0.034). In both groups of patients, there was an increase of IL-6, IL-8, IL-10, IL-17, IL-18, IL-1ra, G-CSF, GM-CSF and VEGF concentrations in tumor supernates and its microenvironment, when compared with the production of cytokines by blood cells, thus indicating to high functional activity of tumor together with its microenvironment. Effect of PA led to increase of IL-2, IL-10, IL-17, IL-1β, IL-1ra, TNFα and IFNγ concentrations in blood cells supernatant which suggested their high ability to produce cytokines. In the group of patients who were 40-60 years old, the stimulatory index of PA (SIPA) for IFNγ production was several times higher than similar index in patients aged 61 years or more. Increase of SIPA for all cytokines in blood cells supernates, in comparison to SIPA of tumor supernates, could be explained by initially high levels of spontaneous cytokine production by the tumor and its microenvironment that are able to promote tumor growth. Therefore, effect of PA upon tumor tissue was not so expressed as its effect upon immunocompetent blood cells. Both tumor and microenvironment maintained high ability of IL-18 production, thus confirming its important role in carcinogenesis. In summary, these findings suggest that circulating immunocompetent cells may serve as an additional factor providing tumor progression, due to their high ability to secrete cytokines.

Keywords

• cytokines
• supernatant
• polyclonal activators
• breast cancer