The data presented in the article reasonably indicate that the immune system responses during the development of autoimmune pathology and in the process of tumor growth are, in fact, autoimmune responses directed at autoantigens of various tissues and organs, and tumor-associated antigens. The latter, in addition to the tumor itself, are also expressed by the cells of normal organs and tissues. At the same time, the differences are characterized by insufficient activity of suppressor cells in the first variant, and enhanced activity in the second variant. One should take into account a potential identity of the mechanisms of lymphocyte responses, both in autoimmune pathology and in oncogenesis. The concept of autoimmunity promoting the tumor development is a fundamentally important point, with regard of the tumor growth biology. In view of medicine, this approach may provide a vector for searching novel drug effects aimed at inhibiting the suppressor activity of regulatory cells, without higher risk of inducing autoimmune disorders. On the basis of available literature data, one may suggest that the formation of autoimmune pathology is caused by the impaired mechanisms of immune tolerance to autoantigens. Moreover, these mechanisms concern both central tolerance and peripheral tolerance. In the first case, T cells bearing high-affinity receptors directed against autoantigens are not subject to negative selection in the thymus and migrate to the periphery, being ready to induce autoimmune processes. At the same time, peripheral T regulatory suppressor cells do not work with respect to suppression of their activity. There is an evident disturbance of the both central and peripheral tolerance mechanisms. In the case of tumor growth, it has been shown that suppression of T regulatory cells results in development of autoimmune pathology, along with inhibition of tumor growth. The recent data from the literature allow us to suggest a targeted reaction of immune cells against tumor-associated antigens, and not against tumor-specific antigens. One should assume that these T cell effectors against tumor-associated antigens also have reached the peripheral tissues after migration from the thymus, without undergoing negative selection. However, their antitumor activity on the periphery could be suppressed by T regulatory cells. Apparently, it should be considered that the immune response to tumor growth exhibited features of an autoimmune response to tumor-associated antigens with induction of its activities by means of T regulatory immune cells.

Preeclampsia/eclampsia during pregnancy and postpartum are the major risk factors for maternal and infant morbidity and mortality worldwide. At the same time, more than 70% of maternal deaths are of neurological origin, i.e., eclampsia, cerebral edema, intracranial hemorrhage and stroke. Generalized endothelial dysfunction caused by placental antiangiogenic factors leads to increased permeability of the blood-brain barrier and impaired autoregulation of cerebral circulation. Previous studies have shown that preeclampsia increases the risk of cerebrovascular and cardiovascular diseases, as well as cognitive impairments, up to evolving dementia in the future. According to a recently proposed neuropathophysiological hypothesis, preeclampsia is considered proteinopathy with impaired autophagy, thus contributing to brain depositions of wrongly folded pathological protein aggregates and antibodies to these proteins. Preclinical and clinical studies have shown that markers of neuroinflammation and neurodegeneration may reflect brain damage before the onset of severe neurological symptoms. However, is not entirely clear if these results correlate with long-term neurological complications. Over recent years, a certain understanding of preeclampsia pathophysiology in a broader sense has been gained. However, etiology and mechanisms of development of central nervous system dysfunction in this disease remain relevant for studies. A detailed systematic analysis of modern literature has been carried out, concerning the search for neuroinflammation and neurodegeneration markers in hypertensive pregnancy-associated disorders. The presented study used the following information databases: PubMed, Scopus, eLibrary, Cochrane Library, MEDLINE for the period from January 2015 to December 2024. This literature review provides information on pathogenetic role of the following neural biomarkers in preeclampsia: monocyte chemotactic protein 1 (MCP-1), brain-derived neurotrophic factor (BDNF), fractalkine (CX3CL1), neurospecific enolase (NSE), S100 calcium-binding protein B (S100B), visinin-like protein-1 (VILIP-1), tau protein (tai), phosphorylated tau protein for threonine 181 (p-tau181), a-synuclein (a-syn), amyloid b-40/42 (A 40/42), glial fibrillary acid protein (GFAP), light chains of neurofilaments (NfL). Usage of appropriate cerebral biomarkers will enable identification of patients at high risk for severe cerebral complications, optimization of their management and treatment during pregnancy, and development of effective strategies to prevent the development of neurological changes in the future.

Chimeric antigen receptor (CAR) T cell therapy shown a promising treatment for haematological malignancies. Although it has successful achievement in hematological malignancies, there are major challenges that remain to be resolved to the broad application. To overcome these obstacles, changes in metabolism during the preparation of CAR T cells increase their therapeutic specificity and potency. Therefore, generation of CAR T cells with manipulated metabolic pathways could beneficially enhance antitumor immunity. Here in this review we summarize the latest advances and new strategies that have been developed to improve the metabolic fitness and antitumor activity of CAR T cells products.

Differentiation therapy is a promising direction in treatment of oncological diseases. It is based on usage of agents that increase the degree of tumour cell differentiation, and thereby reduce the malignant potential of the neoplasm. Such effects are shown for the acetyl-amide form of the synthetic peptide HLDF-6. The peptide was previously found to reduce the relative content of low-differentiated cells in breast cancer biopsy specimens. However, the mechanisms of the peptide's effect on tumour cells and its microenvironment remain unknown. The effect of this peptide may be associated with altered functional activity of the tumour. The aim of our study was to investigate the effect of acetyl-amide form of synthetic HLDF-6 peptide on cytokine production by bioptates of invasive non-specific breast carcinoma. Morphometric analysis of bioptates obtained from 40 women with invasive breast carcinoma of nonspecific type before and after exposure to acetyl-amide form of synthetic peptide HLDF-6 was performed. To evaluate the effect of this peptide, we proposed an estimated index for HLDF-6 effect being expressed in conventional units (c. u.). The index of HLDF-6 influence of 0.9 с. u. and less is accepted as a significant effect. Depending on the index value, the patients were divided into two groups. The first group consisted of 27 patients with a significant effect of the studied peptide, the second group consisted of 13 patients without a significant effect. Concentrations of TNFa, IFNg, VEGF, G-CSF, GM-CSF, MCP-1, IL-6, IL-8, IL-10, IL-17, IL-18 and IL-1b were determined in parallel in supernatants of bioptates before and after incubation with the studied peptide using the enzyme immunoassay technique. The influence (effect) index, IE-HLDF-6-cytokine, expressed in conventional units (c. u.), reflected the effect of the acetyl-amide form of the synthetic HLDF-6 peptide on cytokine production by tumour bioptates. The study showed that spontaneous production of GM-CSF in the first group was significantly lower than in the second group. However, the concentration of this cytokine under the influence of HLDF-6 peptide significantly increases in group I in comparison with group II, as evidenced by statistically significant difference in IEHLDF-6-cytokine. According to the results of ROC-analysis, a good model quality was obtained in the study of IE-HLDF-6-GM-CSF and relative content of low-differentiated cells, which may serve as a basis for using this index as a cut-off point used for selection of patients who may be candidates for differentiation therapy with acetyl-amide form of synthetic peptide HLDF-6.

Luminal HER2-negative subtypes of breast cancer have always attracted oncologists due to their sensitivity to low-toxicity hormone therapy. The emergence of new inhibitors of cyclin-dependent kinases has allowed hormone therapy to achieve optimal control of tumor growth, being prescribed even for visceral lesions. Recent advances in this area have provided novel mode of hormonal therapy as the first-line standard for extended HR⁺/HER2breast cancer. Evaluation of the relationship between tumor progression and immune surveillance was more often associated with the triple-negative subtype characterized by relatively high levels of mutational load and tumor-infiltrating lymphocytes. However, data from some studies suggest a possible relationship between immunity and luminal types of breast cancer. On the basis of these conclusions, the aim of our work was to evaluate different immunological and clinical factors in view of effectiveness of combined endocrine therapy with CDK4/6 inhibitors in metastatic luminal HR⁺/HER2breast cancer, primarily in the context of assessing immune deficiency conditions by the levels of T-cell receptor excision circles (TREC) and k-deletion element of B cells (KREC). The study included 51 patients with luminal HER2-negative breast cancer who received combined endocrine therapy with CDK4/6 inhibitors. The results of the study indicated a decrease in TREC levels with increasing patients’ age. A decrease in the absolute number of TREC was noted in peripheral blood of patients with worse treatment outcomes, i.e., insufficient response to therapy, rapid progression or death, along with significant intercorrelation between lethal outcomes and low levels of B cell k-deletion element (KREC) thus suggesting an important role of these immune factors in clinical prognosis. Hence, we consider prognostic significance of T cell receptor excision rings in the patients’ peripheral blood. This factor may affect treatment outcomes and survival rates.

Earlier it was shown that actively proliferating tumors with Ki-67 positive cells > 20% are more frequently detected in breast cancer patients (BC) with high serum levels of autoantibodies against estradiol and progesterone (IgA1-E2 and IgA1-Pg), and less common in BC with high levels of corresponding antiidiotypic autoantibodies (IgG2-E2 and IgG2-Pg). The genetic factors for development of these auto-antibodies are still unknown. The purpose of this study was to search for associations between polymorphic loci of the IL1A (rs1800587), IL1B (rs16944), IL6 (rs1554606, rs1800795, rs1800796), IL10 (rs1800896) and TNFA (rs1800629) genes and serum levels of IgA₁-E2, IgA1-Pg, IgG2-E2, IgG₂-Pg as compared with tumor levels of Ki-67positive cells in BC patients. Antibodies and antiantibodies specific to steroid hormones were assessed by means of ELISA technique, being studied in 661 BC stage I patients, and in 741 patients with stage II-IV disease. Single nucleotide polymorphisms of cytokine genes were determined by PCR technique in DNA isolated from lymphocytes. Ki-67-expressing cells were detected using immunohistochemical technique in tumor samples of 484 stage I BC patients, and in 551 patients with disease of II-IV stage. Higher levels of Ki-67 positive tumor cells were found in patients with stages II-IV breast cancer carrying GG genotype of IL6 gene (rs1800796) more frequently than in patients with the CG genotype (63.3% vs. 48.6%, p = 0.02). Three immunological phenotypes have been found according to individual combinations of studied idiotypic and antiidiotypic antibodies differently associated with tumor proliferation in BC patients (stage II-IV). Highly proliferating tumors (Ki-67 positive cells > 20%) were found in 61.5% BC patients with “neutral” immunological phenotype; in 47.3% BCP with “inhibition” phenotype (p = 0.02 vs. “neutral”), and in 71.2% (p = 0.047 vs. “neutral”, p < 0.001 vs. “inhibition”). The frequency of BC patients with any not changed from I to II-IV stages of the disorder. The “stimulating” phenotype was found more often in carriers of the GG IL6 genotype (rs1800796) than in persons with CG genotype (26.8% vs. 19.1%, p = 0.028). In conclusion, immunomodulation of tumor proliferation by idiotypic and antiidiotypic antibodies specific to steroid hormones was associated with functional polymorphism rs1800796 of the IL6 gene.

Colorectal cancer (CRC) is among the most common oncological diseases in the world, associated with a high mortality rate. Recently, immunotherapeutic approaches to the treatment of CRC have been developed, which have enabled achievement of long-term and stable remission in a certain group of patients. The success of immunotherapy depends on the immune processes associated with oncogenesis in the colon. The key role in modulating immune environment of the tumor is played by the activity of genes regulating differentiation and functions of immune cells, as well as by a variety of microRNAs that perform posttranscriptional expression control of target genes. In this regard, the aim of our work was to study the expression profiles of immune-associated genes and microRNAs to determine the immune signaling mechanisms of colon cancer and search for potential therapeutic targets. The study included 18 persons (12 women, 6 men, median age – 66 years) diagnosed with colon cancer, having been treated at the National Medical Research Center of Oncology in 2018-2019. All tumors had microsatellite instability status. The transcription profiles of microRNAs and immune response genes were determined by next-generation sequencing. The study has revealed 28 differentially expressed microRNAs in the tumor tissues, including 15 microRNAs with increased expression and 13 microRNAs with decreased expression. Of the 395 genes examined, 156 were differentially expressed, including 62 genes with increased expression and 94 genes with decreased activity. Identification of cell populations based on the transcriptional pattern of tumors has discerned four types of immune cells: neutrophils, B lymphocytes, CD8⁺T lymphocytes, and M1 macrophages. Neutrophils were the most common cell type (16 of 18 samples). A stepwise analysis of possible relationships between transcriptional patterns allowed us to select 713 miRNA-mRNA pairs. After filtering by validated interactions, 24 such pairs were found. On this basis, a miRNA-mRNA interaction network was constructed, which could be involved into the regulation of multiple immune signaling mechanisms and cell cycle control. Most of the revealed signaling pathways contained CDK1, for which therapeutic inhibitors are known, being at different stages of clinical trials. The possibilities of influencing CDK1 described in the present work may be used for further clinical studies and development of therapeutic strategies employing selective molecular suppression of immunemediated carcinogenesis in colorectal cancer.

The increasing incidence of infertility determines relevance of studying various cellular factors, including immune cells, in pathogenesis of this disorder. In cases of infertility, some changes are described in NK cell activation in decidual and peripheral blood cells, as well as in representation of NKT cells and T lymphocytes in uterus at miscarriage (MC). NK cells and NKT cells are characterized by expression of activating receptor NKG2D and a receptor for immunoglobulin G Fc-region CD16. Distinct populations of T lymphocytes express NKG2D. The aim of the present study was to analyze the expression of CD16 and NKG2D by NK cells, NKT cells and NKG2D receptor by peripheral blood T lymphocytes. We examined 60 women with infertility. The control group consisted of healthy non-pregnant fertile women (n = 17). Mononuclear cells were obtained from peripheral blood and treated with monoclonal antibodies to CD45, CD14, CD3, CD56, CD16, NKG2D. The intensity of NKG2D receptor expression on peripheral blood NKT cells in patients with primary infertility proved to be lower than in healthy non-pregnant fertile women. This difference may be caused by the absence of an embryo implantation in previous history of primary infertility and, accordingly, lacking influence of cytokines and cellular microenvironment specific for first trimester of pregnancy. In patients with secondary infertility and miscarriage (MC), the relative numbers of CD16⁺NK cells and CD16⁺NKG2D^-NK cells in peripheral blood were reduced when compared to the women with secondary infertility without history of MC. Relative numbers of CD16⁺NK cells and CD16⁺NKG2D^-NK cells in peripheral blood were also reduced in patients with secondary infertility and MC compared to patients with primary infertility and to healthy non-pregnant fertile women. CD16 expression intensity of NK cells was shown to be reduced in subgroup of women with secondary infertility and a history of MC compared to control group and to women with secondary infertility without a history of MC. No differences in NKG2D expression by T lymphocytes associated with infertility were found. Reduced CD16 expression by NK cells of women with secondary infertility and MC may reflect the impaired functional differentiation of NK cells associated with this condition.

Our objective was to evaluate the level of cytokines and growth factors in peripheral blood in women with pregnancy failure, including women with detectable antiphospholipid antibodies (APhA). Eighty-eight women aged 22 to 45 years were examined. The patients were divided into groups: control group included women with physiologically normal pregnancy; the main group consisted of women with a history of one or more cases of miscarriage. The main group was subdivided into subgroups depending on the presence or absence of APhA in blood serum. The APhA-positive subgroup and a history of miscarriage was then subdivided into subgroups with high and low levels as measured by ELISA test. We evaluated the levels of antibodies to cardiolipin and beta2-glycoprotein-I, and the concentrations of cytokines (IL-1b, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12(p70), IL-13, IL-15, IL-17, Eotaxin, bFGF, G-CSF, GM-CSF, IFNg, IP-10, MCP-1 (MCAF), MIP-1a, PDGF-BB, MIP-1b, RANTES, TNFa, VEGF) in their blood serum and plasma samples. Women with a history of miscarriage, either negative or positive for APhA, are at risk, having an increased contents of proinflammatory cytokines in peripheral blood. Moreover, the women with APhA and a history of miscarriage comprise a group at risk for developing preeclampsia, having increased VEGF, IL-6 and IL-8 levels in peripheral blood. AFAs, regardless of their level, may contribute to development of the pathological process, since an imbalance of proand anti-inflammatory cytokines has been shown in women with APhA, due to a decrease in compensatory anti-inflammatory response. Women with a history of miscarriage and AFAs are more susceptible to placental disorders. Determination of a complex of immunological markers enabled us to clarify various pathophysiological pathways of obstetric pathology, including miscarriage of pregnancy. In this regard, the promising approach would be a search for the most significant combinations of proand anti-inflammatory cytokines, growth-promoting and angiogenic factors with both positive and negative regulation.

Bacterial vaginosis is a serious public health problem due to the increased risk of sexually transmitted infections and development of various obstetric and gynecological disorders. The local production of cytokines and antimicrobial peptides in the vagina plays an important role in regulation of genital tract immunity. The aim of the present study was to compare microflora and factors of nonspecific protection in vaginal environment in women with bacterial vaginosis before and after treatment. Our study included 110 patients with bacterial vaginosis (main group) and 26 conditionally healthy women with vaginal normocenosis (control group). The Amsel clinical criteria were determined, the vaginal microbiocenosis was studied using a molecular biology method using the Femoflor-16 test system. The contents of IL-6, IL-8, TNFa, IL-10 cytokines and acute phase proteins of C-reactive protein, C3-complement component and lactoferrin in vaginal secretions were studied by ELISA test systems. Methods of variation parametric and nonparametric statistics were used for statistical analysis. Statistically significant differences were taken at a confidence level of p < 0.05. Bacterial vaginosis was found to be accompanied by increased levels of IL-6, IL-8, TNFa and IL-10 (by 5.6, 5.5, 6.8, 4.1 times, respectively), and C-reactive protein by > 10 times, along with decrease in the C3 component of complement, and lactoferrin by 2.2 and 1.4 times, respectively, in the vaginal discharge (p < 0.001). After treatment of vaginosis, the patient groups with initial local dominance of obligate anaerobes (Sneathia spp. / Leptotrichia spp. / Fusobacterium spp., Megasphaera spp. / Veillonella spp. / Dialister spp., Atopobium vaginae and Mycoplasma hominis) exhibited increased levels of IL-6, TNFa and IL-10, along with low content of the C3 component of complement and lactoferrin. Thus, post-treatment preservation of low C3 component and lactoferrin levels may serve as a marker of recurrent bacterial vaginosis.

Timely diagnosis of immunodeficiency states (IDS) in children still presents significant issues, especially, when they develop due to failure of the thymus. Thymus pathology may be caused not only by fetogenetic reasons, but also by premature age-related involution caused by the impact of “excessive” stress factors such as infection, continuous hunger, chemotherapy, radiation exposure (including X-ray studies), prolonged hypoxia, tuberculosis infection, tumor growth, etc. Secondary involution processes in the thymus may lead not only to its sub-atrophy (microthymus), but also be accompanied by petrification, leading to irreversible loss of functioninal parenchyma. More often than any mentioned reasons, such deleterious effects are assigned to viral infections, especially in cases of proven thymic infections, with SARS-CoV-2 virus taking a significant place. Clinical manifestations of immune deficiency can persist for several months (or more), from the moment of past pathogenic exposure (usually, infectious factor), over the time required for evolving a petrified structure and its spread. Such pronounced pathomorphosis of the thymus gland is uncommonly diagnosed during the lifetime by means of ultrasound examination. This is, mainly, a pathomorphological finding, when, for example, a life-threatening infection is a manifestation of the already evolved IDS. The immediate cause must be sought via the preceding monitoring. This is a relevant reason for identifying a risk group of such patients performed at the pre-clinical stage of the above-mentioned conditions, with subsequent provision of these patients with both timely diagnostics, conservative drug support (or radical treatment), and a safe epidemiological environment. Our results suggest a significant diagnostic role of ultrasound examination of the thymus for early verification of its critical involution (i.e., sub-atrophy), especially, persisting changes and signs of petrification. Upon revealing these signs in the patient, being combined with high infectious, immune-mediated morbidity and low concentration of TREC copies in nucleated blood cells in a dry drop preparations (less than 500 copies), specific recommendations are offered for the final exclusion of highly probable immunodeficiency disorder.

Currentstudies of autoimmunityprocesses areaddressing specific processes involving mitochondria, i.e., altered intracellular signaling including the generation of ROS and release of proteins from mitochondria to the cytoplasm, thus activating apoptosis. These functions of mitochondria are usually associated with disturbed bioenergetic functions and excessive production of H₂O₂. Currently, a new area is actively developing, i.e., potential participation of mitochondria in the immune response. Therefore, the aim of the present study was to evaluate the dynamics of apoptosis factors and autophagy associated with mitochondria of CD4⁺T cells in autoimmune thyroiditis (AIT). The study was performed with CD4⁺T cells of AIT patients and healthy donors obtained by magnetic separation. Apoptosis and autophagy were assessed by flow cytometry. Western blotting was used to analyze autophagy marker proteins (p62, LC3I/II, mTOR kinase), and apo ptosis regulator Bcl-2 in CD4⁺T lymphocytes of the patients and donors. The state of mitochondria in CD4⁺T lymphocytes was assessed by confocal microscopy. Using an experimental model with increased H₂O₂, we showed that ROS activate LC3 protein in cells of patients with AIT along with accumulation of autophagic adapter protein p62, as registered on the outer mitochondrial membrane. An increased level of mitophagoses was found in CD4⁺T cells from the AIT patients. On the basis of these data, one may assume that H₂O₂ causes activation of mitophagy in CD4⁺T cells of patients with AIT, and the development of oxidative stress with excessive production of ROS leads to irreversible damage to mitochondria, which causes a decreased apoptotic activity followed by development of secondary necrosis of CD4⁺T lymphocytes in AIT, making them cytotoxic. Accumulation of such cells in the thyroid tissue may lead to impaired apoptosis in thyrocytes and, as a consequence, to secondary necrosis, thus resulting in development of autoimmune response. The obtained data require additional studies, since the detection of CD4⁺T lymphocytes prone for apoptosis or necrosis in patients with AIT may be used as a diagnostic criterion for prediction of inflammatory conditions.

Among the numerous pathogenetic factors of age-related macular degeneration (AMD), special attention has been recently paid to endothelial dysfunction (ED), since the vascular endothelium is an important internal component of the the hematoretinal barrier (IBRB) providing immunological homeostasis of the retina. The study of inflammatory endothelial activation markers seems relevant in terms of understanding the mechanisms of disease development, potentially contributing to the development of pathogenetic therapy at early and intermediate stages of AMD as well as secondary prevention of its complications. The aim of the present: study was to determine sICAM-1, sVCAM-1, sE-selectin, sP-selectin and MCP-1/CCL2 in blood serum (BS) and tear fluid (TF) of patients with initial (AREDS2) and intermediate (AREDS3) stages of AMD. The study was performed by flow cytometry (CBA) with BD FACS Canto II flow cytometer, USA), using a diagnostic panel based on compatible simplex Flow Cytomix^TM test systems (Bender Med System GmbH, Germany) to determine sICAM-1, sVCAM-1, sE-selectin, sP-selectin and MCP-1/CCL2 thus allowing their simultaneous detection followed by data processing in the FlowCytomix Pro v. 6.0 package (BenderMed Systems GmbH, Germany). We have revealed a tendency to increased serum sVCAM-1 in the AREDS3 group compared to the reference values. When studying tear fluid in the AREDS2 group, a significant increase in MCP-1, sE-selectin concentrations was found (p < 0.05), along with a tendency to increased local production of sICAM-1 and sP-selectin (p = 0.05) against normal levels. Significant shifts in the AREDS3 group concerned three 3 factors in tear fluid, i.e., sICAM-1, sE-selectin and sP-selectin, that exceeded control levels by 2.5, 5 and 2 times, respectively (p < 0.05). The obtained data are important because they presume a role of sICAM-1, sVCAM-1, sE-selectin, sP-selectin, MCP-1/CCL2 in pathogenesis of the disorder and allows us to suggest a compromised state of blood retinal barrier, thus requiring supplementation of AMD therapy with angioprotectives, antiinflammatory drugs, and needs further studies.

Breast cancer (BC) is the most common malignant neoplasm in women. Adoptive immunotherapy (AIT) using activated lymphocytes is a promising approach to the treatment. Patient O., 63 years old, was diagnosed in October 2021 with infiltrating ductal carcinoma of left breast T3NxM0, Grade 2, triple negative subtype, CHEK-2 associated. According to PET/CT, the tumor size was 43 ´ 21 mm. AIT with cytokineinduced killers (CIK) was administered. In order to produce CIK, mononuclear cells were isolated from peripheral blood and cultured in presence of cytokines for 10-14 days. AIT was performed by intradermal injections paravertebrally once a week up to present date. In the course of AIT, PET/CT, MRI, ultrasound and immunophenotyping of blood lymphocytes were performed. 7 courses of AIT were administered since November 2021. Six months after starting AIT, positive dynamics was noted as proven by PET/CT data: a decreased activity of tumor in left mammary gland (LMG) with SUVmax of 16.76 (previously, SUVmax 28.74) while maintaining the size. Moreover, previously identified signs of osteoblastic changes in spine at Th12 level were not detected. According to PET/CT results in November 2022, a slight increase in size of LMG formation up to 49 ´ 35 mm (SUVmax, 16.82) was noted, while an area of the radiopharmaceutic accumulation was detected in the body of the L2 vertebra and sigmoid colon. Radical mastectomy was performed In early December 2022. The tumor size was 5.3 cm, the resection margin was free of tumor cells, metastases were found in 2 of 14 lymph nodes. In order to prevent relapse, AIT was continued: 790 million CIKs were administered during a year. According to MRI data in March 2023, there was no relapse. In August 2024, the lesion in the ileum still remains. The median overall survival of patients with TNBC is 10.2 months. The average life expectancy of patients with metastases is less than 1 year. In the presented clinical case, 34 months have passed since the diagnosis, thus indicating an effective combination of AIT with surgical treatment. We conclude that AIT CIKs has a high potential for treatment of patients with TNBC.

The role of cytokines in regulating the immune response and tumor progression is an important aspect of studies in oncology. B16 melanoma is characterized by an aggressive course and a high level of metastasis, which requires a deep understanding of the mechanisms involved. The purpose of this study was to study the level of cytokines in the blood plasma of mice with B16 melanoma. The experiment used C57BL/6 mice injected with B16-F10 melanoma cells. The animals were divided into two groups: control and experimental. Levels of key cytokines such as IFNg, TNFa, IL-6 and IL-10 were monitored for 21 days using enzyme-linked immunosorbent assay (ELISA). The results of the study showed a significant increase in the level of IFNg and TNFa cytokines in the blood plasma of mice from the experimental group compared to the control group. It should be noted that both IFNg and TNFa play a key role in stimulating macrophages and neutrophils for more effective killing of tumor cells. This cytotoxic response helps suppress tumor growth and metastasis. Elevated levels of IL-6 indicate the development of an inflammatory response. Although this cytokine at certain doses may reduce inflammation, excessive IL-6 can promote the growth and more aggressive behavior of tumors. Reduced levels of IL-10 can increase inflammation and weaken the body’s immune response against tumors. Thus, the balance between various cytokines plays a crucial role in regulating the immune response to cancer cells and determines the nature of tumor progression. At the same time, the level of IL-10, a cytokine with antiinflammatory properties, was reduced in the experimental group, thus indicating an imbalanced regulation of immune response. Thus, the data obtained demonstrate that development of B16 melanoma is associated with significant changes in the blood plasma cytokine profile which may play a key role in the pathogenesis of the disease. These results highlight the importance of further research to develop new therapeutic strategies aimed at modulating the cytokine response in melanoma.