Tumor microenvironment: the formation of the immune profile

Tumor microenvironment (TME) is formed as a result of interaction and cross-linking between the tumor cell and different types of surrounding cells. Recent studies have shown that the tumor reprograms the microenvironment so that TME promotes the development of primary tumors, their metastasis and becomes an important regulator of oncogenesis. Under the influence of the tumor, the immune profile in the TME undergoes significant changes, “editing". An immunosuppressive network is formed, which suppresses the activity of the main effector of cellular immunity — T lymphocytes. T cells in TMA are in a state of anergy and exhaustion. T cells in TME are characterized by increased expression of inhibitory receptors, decreased secretion of cytokines and cytolytic activity. Blocking inhibitory receptors with specific antibodies can lead to the restoration of the functions of exausted T cells. Therefore, the restoration of the functional activity of T lymphocytes is one of the important strategies in cancer immunotherapy. The formation of the immune profile is influenced by genetic aberrations accumulating in the tumor. They play an important role in creating a specific, characteristic only for this tumor immune environment in the TME. Genetic changes in tumor cells lead to phenotypic and functional rearrangements of lymphocytes, which allows the tumor to escape the reaction of immune cells. Since many tumors occur after prolonged inflammation or exhibit characteristics of chronic inflammation as they progress, inflammation is considered an important factor in the formation of immune profile in TME. Immune infiltrates from different human tumors associated with inflammation may contain valuable prognostic and pathophysiological information. Macrophages in the TME now began to be regarded as descriptive marker and as a therapeutic target. One of the main mechanisms by which tumor cells reprogram surrounding cells is the release of exosomes — small vesicles that carry and deliver proteins and nucleic acids to other cells. When exosomal cargo is absorbed, molecular, transcriptional and translational changes occur in the recipient non-tumor cells in the TME. Therefore, tumor exosomes are an effective means by which the functions of immune cells in TME are purposefully changed. Thus, along with individual molecular and genomic testing of the tumor, attention should be paid to a deeper analysis of the immune profile of TME. It is a large resource of biomarkers and targets for immunotherapy

Photovoltaic properties of nanocomposites of cadmium alkanoates with semiconductor nanoparticles

Ionic liquid crystals of metal alkanoates in the smectic phase (+150оС) can be act as nanoreactors for the chemical synthesis of nanoparticles (NPs) of different types: semiconductors, metal and core/shell. The technology of chemical synthesis of nanoparticles directly in the matrix of an ionic liquid crystal contributes to the fact that the matrix acts as a stabilizer of nanoparticles, which leads to a small dispersion of the sizes of NPs, and the content of NPs in the matrix can reach large concentrations (up to 8 mole%) [1]. The smectic liquid crystal phase of the nanocomposite retains its layered structure under conditions of slow cooling. By such a way, anisotropic glass nanocomposites with layered smectic-like structures are formed at the room temperature with incorporated nanoparticles inside the matrix. The nanocomposits exhibits anisotropy of electric conductivity, which is directed mainly along cation-anion layers in the smectic-like matrix. The conduction mechanism is of ionic type with the activation energy ~0.8 eV for the nanocomposites with semiconductor NPs.For the first type, we detect the photovoltaic effect both in a pure matrix and in the nanocomposites with semiconductor NPs, in "sandwich"-like cells under illumination of samples perpendicular to the cation-anion layers by a lamp that emits in a wide range of wavelengths in the ultraviolet - blue diapason of the spectrum. Different dependences of short-circuit current are obtained from the temperature in LC mesophase and in anisotropic glasses. The magnitude of the short-circuit current increases in 3 orders of magnitude in the nanocomposites compared with the short-circuit current of the pure matrix, and the relaxation time is significantly reduced. It is established that photo-stimulated charge distribution occurs due to photo-generation of ions and transmission of electric field along the cation-anion layers of the matrix [2].[1] Zhulai D.S, Bugaychuk S.A., Klimusheva G.V., Mirnaya T.A., Asaula V.N., Handziuk V.I ., Vitusevich S.A. Structural characteristics of different types of nanoparticles synthesized in mesomorphic metal alkanoates // Liquid Crystals, DOI: 10.1080/02678292.2016.1276979 (2017)[2] Zhulai D, Kovalchuk A, Bugaychuk S, Klimusheva G, Mirnaya T., Vitusevich S. Photoconductivity of ionic thermotropic liquid crystal with semiconductor nanoparticles // Journal of Molecular Liquids, DOI: 10.1016/j.molliq.2017.12.097 (2017

Photovoltaic properties of cd-based ionic liquid crystals with semiconductor nanoparticles

The photovoltaic effect in pure cadmium-alkanoate matrices and in their nanocomposites with semiconductor CdS nanoparticles (NPs) was revealed and investigated. The main mechanism of the phenomenon is the Dember effect, in which the internal field of non-equilibrium charge carriers is formed due to a significant difference in the mobility of positive and negative charges. NPs synthesized in the matrix lead to a significant increase in the concentration of the photo-generated electrons and thus to an increase in the photo-electro-driving force in the material. The magnitude and kinetics of the photocurrent for nanocomposites substantially depend on the content of only a small amount (2 − 4 mol. %) of NPs

Photoconductivity of ionic thermotropic liquid crystal with semiconductor nanoparticles

The characteristics of photocurrent are investigated in new nanocomposites of cadmium octanoate with semiconductor nanoparticles (NPs) as well as in pure matrix of the cadmium octanoate. CdS NPs are synthesized inside the cadmium octanoate matrix during one-step chemical reaction. The photoconductivity in these nanocomposites has been detected in wide temperature range. The photocurrent exhibits nonlinear behavior over all different mesophases of the nanocomposites. Two types of near-electrode processes that occur depending on the value of applied voltage are considered to explain the nonlinear dependence of the current-voltage characteristics

SIGNIFICANCE OF Treg CELLS FOR ADENOSINE-MEDIATED IMMUNE SUPPRESSION IN COLORECTAL CANCER

At the present time, immunosuppressive role of extracellular adenosine in carcinogenesis is actively investigated. Colorectal cancer is one of the most common types of malignant neoplasms in Russia and worldwide, but the role of mediators of adenosine-dependent immunosuppression, such as CD39 (that hydrolyze ATP to adenosine), CD73, A2AR, is not yet clear in patients with colorectal cancer. The levels of specific mRNAs for A2AR, ectonucleotidase CD39, and CD73 genes were assayed in white blood cells of the patients with colorectal cancer. The results have shown that the CD39 mRNA content is increased in the patients with colorectal cancer in the course of the disease progression. Meanwhile, no significant difference for CD73 gene expression was found between the patients and healthy donors. Moreover, an increase in A2AR mRNA expression was noted for the patients with advanced colorectal cancer, thus presuming potential activation of adenosine-A2AR-mediated immunosuppressive mechanism. Furthermore, the CD39 expression on T cells was elevated in parallel to the cancer progression. The most significant changes in CD39 expression were observed for both T helper and Treg cell populations at the late stages of colorectal cancer. Similarly, a direct correlation was revealed between CD39 expression on CD4+CD25+CD127lo/-Treg cells, and changes of A2AR mRNA levels in leukocytes from the cancer patients

EVALUATION OF THE CONTENT OF CD4+CD25+CD127LOW REGULATORY T CELLS AND THEIR FUNCTIONAL STATUS ACCORDING TO THE EXPRESSION OF CTLA-4 AND CD39 MOLECULES IN PATIENTS WITH RHEUMATOID ARTHRITIS

Objective. To study the content of the suppressor population of regulatory T cells (Treg) according to the expression of CD4, CD25, CD127 molecules, as well as the expression of two functional molecules (CTLA-4 and CD39) in patients with rheumatoid arthritis (RA). Material and methods. 16 samples of peripheral blood of RA patients and 10 blood samples of healthy donors were analyzed. All patients received disease-modifying anti-rheumatic drugs. The expression level of all studied molecules was assessed by flow cytofluorometry. Results. The content of T-helpers in peripheral blood of RA patients was 36.3 ± 7.1% of the total number of lympho- cytes and was lower than that in the control (43.8 ± 6.2%, p<0.05). The number of activated CD4+CD25+ T cells in these patients increased twofold (RA 23.7 ± 9.8%, control 11.1 ± 2.0% of the number of CD4+ T cells, p<0.05). The relative amount of CD4+CD25high (RA 2.7 ± 1.0%, control 1.5 ± 0.8%) and CD4+CD25highCD127low/- (RA 2.5 ± 1.0%, control 1.6 ± 0.9% of CD4+ T cells) Treg cells in RA patients was significantly higher than that in healthy individuals (p<0.05). The expression of the CTLA-4 negative regulatory molecule and CD39 ectonucleotidase by Treg cells of RA patients did not differ from the control. Conclusion. The study demonstrated that RA is characterized by an increased content of Treg cells of CD4+CD25high and CD4+CD25highCD127low phenotypes rather than CD4+CD25+CD127low, as well as by the control-like expression of CTLA-4 and CD39 functional molecules by Treg cells