Phenotypic and functional characteristics of dendritic cells and contents of suppressor cell populations in peripheral blood of breast cancer patients.

The progression or the appearance of distant metastases in breast cancer (BC) is influenced by a variety of antitumor immune response suppression mechanisms. In this paper we study circulating dendritic cells (DC) and the suppressor cell populations in peripheral blood of breast cancer patients. The study of phenotypic and functional properties of DCs was performed in the samples of intact and TLR-stimulated whole blood from breast cancer patients and healthy women by multicolor flow cytometry. To determine the suppressor cell population among lymphocytes multicolor panel comprising markers CD 4, CD 25, CD 127, FoxP3 was used. It is showed that the formation of secondary foci of tumor growth in patients was accompanied by disturbances of the functional activity plasmocytoid DC and accumulation of cells with immunosuppressive functions.

[Features of functional activity of dendritic cells in tumor growth].

During recent years much data, accumulated on biology, function and role of dendritic cells (DC) in cancer development, in a new way allow assessing their role in disease process. Identification of features of DC functional state as well as their interaction and influence on the immune cells in tumor growth can be used as a basis for a new approach to cancer therapy enhancing standard therapy efficacy. The review analyzes different mechanisms of escaping of tumor cell from immune surveillance involving DC as one of the main participants of antitumor immune response. Also the prospects of using DC for vaccination are discussed. DC can be promising target for therapeutic strategies and also can be used for formation of antitumor response and cell therapy.

Dendritic Cells Transfected with a DNA Construct Encoding Tumour-associated Antigen Epitopes Induce a Cytotoxic Immune Response Against Autologous Tumour Cells in a Culture of Mononuclear Cells from Colorectal Cancer Patients.

Significant effort has been devoted to developing effective cancer vaccines based on dendritic cells (DCs) loaded with various tumour antigens, including DNA constructs that carry sequences of tumour-associated antigens (TAAs). Such vaccines efficiently and selectively activate the T cell immune response. In this study, we describe a method to induce an antitumour immune response in mononuclear cell (MNC) cultures from colorectal cancer patients using DNA-transfected DCs encoding TAA epitopes of carcinoembryonic antigen, epithelial cell adhesion molecule and mucin 4. DCs were obtained from peripheral blood monocytes of colorectal cancer patients. Magnetic-assisted transfection was used to deliver the genetic constructs to DCs. To assess the potency of the immune response, the antitumour cytotoxic response was assessed by lymphocyte intracellular perforin and the MNC cytotoxic activity against autologous tumour cells. We showed that polyepitope DNA-transfected DCs enhanced MNC antitumour activity, increasing tumour cell death and the percentage of perforin-positive lymphocytes. In addition, DNA-transfected DCs elicited a cytotoxic response that was as efficient as that of tumour lysate-loaded DCs. Taken together, the data suggest that it is feasible to induce an antitumour immune response in colorectal MNCs using transfected DCs. Thus, the DNA construct reported in this study may potentially be used in therapeutic and prophylactic DC-based vaccines.

Effect of mature dendritic cells primed with autologous tumor antigens from patients with epithelial ovarian cancer on stimulation of the cytotoxic immune response in culture of mononuclear cells.

For modulation of antitumor cytotoxic activity of mononuclear cells in vitro, autologous dendritic cells loaded with tumor lysate antigens were cultured with peripheral blood mononuclear cells from patients with epithelial ovarian cancer in the presence or absence of IL-12 and IL-18. The efficiency of modulation was evaluated by cytotoxic activity of mononuclear cells against autologous tumor cells, by the production of IFN-γ, IL-4, and by the count of perforin-containing lymphocytes. It was demonstrated that dendritic cells stimulated cytotoxic immune response in mononuclear cell culture. Maximum induction of cytotoxic activity of mononuclear cells was attained in case of dendritic cells combination with IL-12 and IL-18 (increased death of autologous tumor cells, accumulation of perforin-positive lymphocytes, enhanced production of IFN-γ).

Effect of lysosomotropic form of amphotericin B on functional state of phagocytes in experimental candidiasis.

Effect of antifungal preparation amphotericin B and its lysosomotropic composition with dialdehyde-dextran on functional state of phagocytizing cells in the dynamics of granulomatous inflammation induced by C. albicans was studied on CBA mice. A stimulating effect of amphotericin B on the production of reactive oxygen species by peritoneal and bone marrow phagocytes was observed, while lysosomotropic form of the antibiotic did not stimulate generation of oxygen radicals.

Structural changes in the liver and content of steroid hormones in the blood and adrenal glands of mice with systemic candidiasis treated with a composition of amphotericin B and dialdehyde dextran.

In CBA mice infected with C. albicans, phasic pattern of granulomatosis development was observed. In all groups, the number of granulomas in the liver was minimum on day 56 after infection. Treatment with free amphotericin B and its composition with dialdehyde dextran (CA) reduced the number of infiltrations and granulomas in the liver, the changes were more pronounced in animals receiving CA. A different pattern of cyclic fluctuations of cortisol content in the blood and adrenal glands and progesterone content in the adrenal gland was observed. By the end of observation (day 84), cortisol content in the blood and adrenals of mice treated with CA was considerably lower than in untreated mice and animals receiving amphotericin B.

Effect of oxidixed dextrans on oxidative and metabolic function of mouse peritoneal macrophages in vitro and in vivo.

We compared the effects of dextrans with a molecular weight of 35 kDa oxidized by chemical (OD(ch)) and radiochemical (OD(r)) methods on oxidative and metabolic functions of peritoneal macrophages from BALB/c mice in vitro and in vivo. It was found that none type of dextrans exhibits chemiluminescent properties. In vitro study showed that OD(ch) had a priming effect on mouse peritoneal macrophages, while OD(r) did not potentiate the oxidative and metabolic response of cells to zymosan. Being injected intraperitoneally, OD(r) more markedly enhanced chemiluminescent response of mouse peritoneal macrophages and reduced their viability than OD(ch). Thus, both dextrans are biocompatible, but in OD(ch) this parameter is higher.

Functional state of pulmonary macrophages after partial hepatectomy in mice.

Partial hepatectomy leads to qualitative and quantitative changes in the pulmonary compartment of the mononuclear phagocyte system during different periods after surgery. These changes have compensatory and adaptive nature because of loss and subsequent partial recovery of the hepatic compartment of the mononuclear phagocyte system.

Effects of modified amphotericin in experimental systemic candidiasis.

Lysosomotropic composition of dialdehyde dextran and amphotericin B had a greater therapeutic effect in mice with systemic candidiasis compared to free amphotericin B. This composition normalized glucocorticoid function of the adrenal glands and decreased the severity of liver destruction at late terms of granulomatous inflammation.