Abstract
Dendritic cells (DCs) belong to specialized pool of antigen-presenting cells with high functional plasticity and manifest with immunostimulatory or immunosuppressive potential depending on sequence and combination of microenvironment stimuli, which determine their differentiation, maturation and activation. The use of antitumor DCs vaccines is based on the ability of DCs specifically activated in vitro migrate for antigen presentation to T- lymphocytes. We studied the components of the tumor microenvironment that are capable of inhibiting DCs migration. The study of the mobility of DCs in Cell-IQ experimental analytical system showed the presence of an inverse correlation of high strength between the average trajectory speed and the level of immunosuppressive factors (ISFs) in supernatants of cultured skin melanoma cells (TGFβ1, IL-10, IL-18, VEGF-A, EGF, FGF, HGF, sFASL (p<0.01). An inverse relation of high force was found between the movement angle of the DCs population and the expression of cancer testis antigens (CTAs) and other tumor- associated antigens (TAAs) on tumor cells (Melan A, tyrosinase, families of MAGE, BAGE, NY- ESO-1 (p<0.01)). The speed of DCs movement in culture system with melanoma cells #894 was 30.10±2.23 μm/h and differed from that in the presence of IL-10 1 ng/ml (10.45±0.52 μm/h), TGFβ1 10 ng/ml (14.32±0.42 μm/h), VEGF 50 ng/ml (18.7±1.89 μm/h) (p<0.05). One can assume that content of this ISFs in the blood is one of the factors determining clinical efficacy of DCs immune therapy.
Highlights
Tumor cells are capable of synthetizing and producing a range of factors with inhibitory effect on the activity of immune cells, among which the effect on dendritic cells (DCs) system is important
We studied the components of the tumor microenvironment that are capable of inhibiting Dendritic cells (DCs) migration
To study the features of the motility of maturing DCs under the influence of products synthesized by melanoma cells, an in vitro system was created which allowed us to co-culture immature DCs (iDCs) with human skin melanoma cell lines (n=8) and to evaluate speed, trajectory and direction of the DCs movement
Summary
Tumor cells are capable of synthetizing and producing a range of factors with inhibitory effect on the activity of immune cells, among which the effect on dendritic cells (DCs) system is important. DCs belong to specialized pool of antigenpresenting cells with high functional plasticity and manifest with immunostimulatory or immunosuppressive potential depending on sequence and combination of microenvironment stimuli, which determine their differentiation, maturation, activation and polarisation. Activation of DCs under the influence of different stimuli of maturation is associated with the development of increased expression of a variety of intracellular and surface molecules providing migration of DCs to secondary lymphoid tissues and interaction with T-lymphocytes. The use of antitumor dendritic cell vaccines is very relevant as it is based on the ability of the DCs, activated in vitro, to migrate to T-lymphocytes for antigen presentation, the study of the tumor microenvironment components forming systemic and local immunosuppression in the patient’s body is able to modify properties of the DCs, reducing clinical efficacy of immunotherapy
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