Мета-анализ был направлен на оценку связи между полиморфизмами rs2107425, rs2839698, rs217727, rs3741219 гена H19 и риском развития рака молочной железы. Поиск публикаций проводили в базах данных Google Scholar и PubMed за последние 13 лет. Ассоциацию оценивали по статистическим критериям отношения шансов (ОШ) с 95% доверительным интервалом (ДИ). Для проведения мета-анализа использовали программное обеспечение RevMan (Cochrane Collaboration, 5.3. Копенгаген). Для оценки связи четырех полиморфизмов rs2107425, rs2839698, rs217727, rs3741219 с риском развития рака молочной железы в мета-анализ были включены 9 исследований случай-контроль с общей выборкой из 6572 пациентов с раком молочной железы и 6968 доноров в контрольной группе. В результате исследования мы наблюдали связь между rs2839698 H19 и риском развития рака молочной железы в аллельной модели (ОШ = 1,33, 95% ДИ: 1,00- 1,76, Pz = 0,005, Pi2 = <0.00001). Кроме того, в рецессивной модели риск развития рака молочной железы также был ассоциирован с мутантным аллелем rs2839698 (ОШ = 1,33, 95% ДИ: 1,03-1,71, Pz = 0,03, Pi2 = 0,05). Значимых ассоциаций с риском развития рака молочной железы полиморфизмов rs2107425, rs217727, rs3741219 не обнаружили. Настоящий мета анализ показал, что полиморфизм rs2839698 H19 ассоциирован с риском развития рака молочной железы. The meta-analysis was aimed to evaluate the association between polymorphisms rs2107425, rs2839698, rs217727, rs3741219 of the H19 gene and the risk of developing of breast cancer. Publications were searched in the Google Scholar and PubMed databases until August 2023. The association was assessed by statistical odds ratio (OR) criteria with a 95% confidence interval (CI). RevMan software (Cochrane Collaboration, 5.3. Copenhagen) was used for the meta-analysis. To assess the association of polymorphisms rs2107425, rs2839698, rs217727, rs3741219 with the risk of developing breast cancer, 9 case-control studies with a total sample of 6572 patients with breast cancer and 6968 donors in the control group were included in the meta-analysis. As a result of the study, we observed an association between rs2839698 H19 and the risk of developing breast cancer when calculating the allelic model (OR = 1.33, 95% CI: 1.00-1.76, Pz = 0.005, Pi2 = <0.00001). In addition, analysis of the recessive model also showed that the risk of developing breast cancer was significantly associated in individuals with a mutation in the polymorphic allele rs2839698 (OR = 1.33, 95% CI: 1.03-1.71, Pz = 0.03, Pi2 = 0.05). When calculating genetic models for the rs2107425, rs217727, rs3741219 polymorphisms, no statistically significant associations with the risk of developing breast cancer were found. The present meta-analysis showed that the H19 rs2839698 polymorphism associated with the risk of breast cancer.

Over the past decade, the use of adoptive immunotherapy has emerged as a promising approach to treatment of various malignancies, including breast cancer. Cytokines are involved in the development, differentiation and homeostasis of the T cells. Despite the similarities in signaling pathways, the γc cytokines shape the T cell responses differently: IL-2 plays a major role in the development and maintenance of the regulatory T cells, while IL15 stimulates the proliferation and cytotoxic functions of the CD8+ T cells and NK- cells that leads to an enhanced antitumor response. It is of interest to study the combined effect of these cytokines in an experiment.

Scientists agree that three-dimensional tumor cell cultures reflect the in vitro biological features of malignant tumors to a greater extent than it is the case with the conventional monolayer cultures. In particular, the results of assessing the effectiveness of anticancer drugs obtained in three-dimensional cell models are considered as more accurate and consistent with the tumor response in vivo, where sensitivity is usually lower than that found in the in vitro experiments. Some of the most developed cellular models are structures obtained using three-dimensional bioprinting, which include not only malignant cells, but also biogels to imitate the chemical and mechanical properties of the extracellular matrix of the tumor.

In this work we studied the effect of different concentrations of interleukin-2 (IL-2) and interferon-γ (IFN-γ) on the proliferation and immunophenotype of lymphocytes obtained from patients with locally advanced breast cancer (stage II-III) after immunomagnetic depletion of regulatory T cells (Tregs) from the general pool of lymphocytes in vitro. The peripheral blood of 11 patients was used as a material. Peripheral blood mononuclear cells (MNCs) were isolated and regulatory T lymphocytes were removed by immunomagnetic separation. After separation, the cells were cultured in a nutrient medium RPMI-1640 with 10% fetal bovine serum (FBS) for 7 days. Lymphocytes were activated on the first day of cultivation with one of the following cytokines: IFN-γ (10 IU/mL), IL-2 (0.1 or 1 μg/mL); IL-2 (0.1 or 1 μg/mL) and IFN-γ together. Lymphocytes without cytokine addition was used as a control. Cells were counted using an automatic counter before addition cytokines and after 2, 4, and 7 days of cultivation with cytokines, and their phenotype was examined. The results showed some phenotypic differences in some elements of cellular immunity between control and experimental samples. Particular attention is paid to the description of changes in the expression of surface markers in the natural killer (NK) subpopulation. It was noted that the proportion of Tregs, despite their preliminary depletion, increased after exposure to cytokines. As a result, the preliminary decrease in the proportion of Treg cells before the stimulation of lymphocytes did not produce the expected effect, therefore the use of depletion in such a methodological mode did not lead to significant results. However, one should not exclude the possibility of inhibiting Tregs by other methods.

Introduction.The actual task of modern adoptive cancer immunotherapy is the selection of the optimal composition of cytokines for ex vivo stimulation of immunocompetent cells for subsequent administration to oncological patients.The purpose of the studywas to compare the effect of interleukin (IL) 2, 7, 15 and their combinations on the proliferation of natural killer cells in breast cancer (BC) patients in vitro.Materials and methods.The research was conducted on natural killer cells isolated by magnetic separation from mononuclear cells of peripheral blood of ten patients with locally advanced BC (stage II). After separation, the cells were cultured at a concentration of 2.5 × 105 cells / ml for 10 days in RPMI 1640 medium supplemented with cytokines at a concentration of 40 ng / ml each in five experimental variants: IL‑2; IL‑7; IL‑15; IL‑7 / IL‑15; IL‑2 / IL‑7 / IL‑15. On the 10th day of cultivation, the phenotype of cells and the cell cycle were studied by flow cytometry. For immunophenotyping of cells, we used monoclonal antibodies to antigens: CD3, CD16 / 56, CD45, CD4, CD19, and CD8. For cell cycle study cells were stained with propidium iodide.Results. On the final 10th day of cultivation the number of living cells expressed as percentage of the seeding numbers were significantly different from control (45.9 %) in samples IL‑2 (86.8 %) and IL‑7 / IL‑15 (85.6 %), IL‑15 (76.4 %), IL‑2 / IL‑7 / IL‑15 (75.8 %). The proportion of natural killers (CD16+CD56+) significantly differed from the control (18.2 %) in samples IL‑2 (45.6 %), IL‑15 (39.9 %), IL‑7 / IL‑15 (36.2 %), IL‑2 / IL‑7 / IL‑15 (35.9 %). The propor‑ tion of natural killer T cells (CD3+ / CD16+CD56+) significantly differed from the control (0.4 %) in samples incu‑ bated with IL‑2 (2.06 %), IL‑15 (2.2 %), IL‑7 (0.9 %), IL‑7 / IL‑15 (1.26 %), IL‑2 / IL‑7 / IL‑15 (2.46 %). All experimental tests also showed a significant increase in the proportion of cells in the S‑phase and increase in the proliferation index (G2 / M + S).Conclusion.The maximum stimulation of the proliferation of natural killer cells isolated from the blood of patients with BC in vitro was obtained by stimulation with IL‑15 alone and in combinations with γc‑cytokines.

The immune system plays an important role in the development and treatment of many cancer types. This fact determined the emergence of numerous immunotherapeutic approaches, including that of adoptive cell therapy (ACT). In this article, we set out to describe the basic methods of adoptive cell cancer therapy, their application and development prospects. The first part of the article deals with the significance of immunotherapeutic methods for cancer treatment and describes the current state of the problem. The main part of the article provides information on the mechanisms of adoptive T cell (unmodified and genetically modified) transfer, the creation of dendritic cell vaccines and cytokine-induced killers (CIK). In addition, a review of recent achievements in the introduction of the aforementioned methods into the clinical practice is carried out. The conclusion is made that adoptive cell therapy can be considered as one of the most promising methods of cancer immunotherapy, which should be optimized for more effective use in the treatment of cancer.