Influence of dietary and lifestyle factors on levels of inflammatory markers (IL-6, IFN-γ and TNF-α) in obese subjects.

Introduction: The low-grade inflammation occurring in obese individuals leads to many diseases, including cardiovascular disease (CVD). Dietary patterns, food groups or nutrients in a well-balanced diet may reduce the level of pro-inflammatory markers and the risk of obesity-related morbidities. Our study aims to describe three cytokines in obese patients in relation to dietary habits, lifestyle and body composition. Material and methods: Serum samples were collected from 84 obese adult volunteer subjects [body mass index (BMI) ≥ 30 kg/m2] to analyze the concentrations of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ). The subjects were tested by bioelectrical impedance analysis (BIA) and completed a three-day food diary and original questionnaire with the FFQ-6 food consumption frequency questionnaire. Results and conclusions: Higher serum levels of IL-6 and IFN-γ were found in patients with atherosclerosis, but the group was too small for a reliable correlation. Subcutaneous but not visceral adipose tissue correlated positively with IL-6 levels. Dietary factors such as amount of sugars, including galactose and sucrose, in the diet and the frequency of consumption of sweet flavored dairy products correlated positively with the levels of IL-6 and TNF-α, while the frequency of alcohol consumption negatively correlated with the level of IL-6. The greater the frequency of sports, the higher was the level of IL-6. In obese individuals, the level of pro-inflammatory cytokines could predispose to atherosclerosis and is associated with dietary factors and lifestyle.

Placental Cannabinoid Receptor Expression in Preterm Birth.

Background: The cannabinoid receptor (CBR) plays a significant role in oogenesis, pregnancy, and childbirth. It might also play a significant role in preterm birth (PTB). The aim of the study was to investigate the association between the expression of the CBR in the placenta and the incidence of PTB. Methods: This prospective, observational, multicentre preliminary study was conducted on placental samples obtained from 109 women. The study included 95 patients hospitalized due to the high risk of PTB. They were divided into two groups: Group 1, where the expression of the CBR1 and CBR1a was analyzed, and Group 2, in which we examined CBR2 expression. The control group, that is, Group 3, consisted of 14 women who delivered at term, and their placentas were tested for the presence of all three receptor types (CBR1, CBR1a, and CBR2). Results: The study used reverse transcription and real-time PCR methods to assess the expression of CBRs in the placental tissues. The expression of the CBR2, CBR1, and CBR1a receptors was significantly lower in the placentas of women after PTB compared to those after term births, p = 0.038, 0.033, and 0.034, respectively. Conclusions: The presence of CBR mRNA in the human placental tissue was confirmed. The decreased expression of CBRs could serve as an indicator in predicting PTB.

Anti-Cancer and Anti-Inflammatory Properties of Black Garlic.

Black garlic (BG) is a fermented form of garlic (Allium sativum L.), produced at precisely defined temperatures, humidities, and time periods. Although garlic has been used for thousands of years, black garlic is a relatively new discovery. There are many bioactive compounds in black garlic that give it medicinal properties, including anti-inflammatory and anti-cancer properties. In our review article, we present scientific studies examining the anti-inflammatory and anti-cancer effects of black garlic. According to research, this effect is mainly due to the reduction in the production of pro-inflammatory cytokines, as well as the ability to scavenge free oxygen radicals and induce apoptosis. In addition, the phytochemicals contained in it have antiproliferative and antiangiogenic properties and inhibit the growth of cancer cells. Black garlic is a valuable source of biologically active substances that can support anti-inflammatory and anti-cancer therapy. Compared to Allium sativum, black garlic has fewer side effects and is easier to consume.

Bioleptin as a useful marker of metabolic status in children with diabetes mellitus type 1.

Introduction: The purpose of our study was tomeasure the level of leptin and biologically active leptin (bioLEP) in children with type 1 diabetes, depending on the duration of diabetes and its degree of metabolic control. Methods: The study included 94 children (58 boys and 36 girls). In a group of children with diabetes, 40 patients were newly diagnosed with type 1 diabetes, 40 children who have diabetes for more than a year (20 with good metabolic control and 20 with poor metabolic control). The control group consisted of 14 healthy children. The serum level of leptin and bioLEP was measured using a sandwich enzyme-linked immunosorbent assay. To our knowledge, this is the first study to describe bioLEP levels among diabetic children with different forms of disease control. Results: Lower levels of leptin were found in children with diabetes compared to healthy children. Furthermore, we found a statistically higher concentration of leptin in the group of children with newly diagnosed diabetes compared to children from the diabetic group with poor metabolic control and lower than healthy children (11.19 vs. 7.84 and 20.94 ng/mL). Moreover, children in the metabolically well-controlled group had statistically lower levels of this hormone (5.11 ng/mL) than healthy children. Leptin concentrations differed significantly between underweight, overweight, and obese children. Discussion: In our study, the level of bioLEP differed significantly between children in the newly diagnosed diabetes group and children in the long-term, poorly controlled diabetes group and healthy controls. Despite many studies published in recent years, many aspects of leptin secretion, action, and mechanisms of its influence on carbohydrate and fat metabolism are still to be clarified. In our opinion, studies evaluating the status of bioLEP in diabetes can also contribute to a better understanding of the mechanisms regulating metabolism.

Health-Promoting Properties: Anti-Inflammatory and Anticancer Properties of Sambucus nigra L. Flowers and Fruits.

Sambucus nigra L. has been used for centuries in traditional medicine thanks to its valuable healing properties. The healing properties result from its high content of biologically active compounds, mainly antioxidants, which contribute to its anti-inflammatory and anticancer properties. In our review, we have presented scientific studies evaluating the anti-inflammatory and anticancer effects of extracts and their components from S. nigra L. flowers and fruits. The results of the research show that the effect of antioxidant phytochemicals contained in their composition reduces the level of free radicals and pro-inflammatory cytokines, prevents mutations that increase the risk of cancer development, and inhibits cell proliferation, induction of apoptosis, and changes in intracellular signaling, consequently inhibiting the growth of malignant tumors and the formation of metastases. Flowers and fruits of S. nigra L. are a valuable source of nutraceutical and pharmacological substances that can support prevention and anti-inflammatory and oncological therapy without negative side effects for the patient.

Garetosmab in fibrodysplasia ossificans progressiva: a randomized, double-blind, placebo-controlled phase 2 trial.

Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by heterotopic ossification (HO) in connective tissues and painful flare-ups. In the phase 2 LUMINA-1 trial, adult patients with FOP were randomized to garetosmab, an activin A-blocking antibody (n = 20) or placebo (n = 24) in period 1 (28 weeks), followed by an open-label period 2 (28 weeks; n = 43). The primary end points were safety and for period 1, the activity and size of HO lesions. All patients experienced at least one treatment-emergent adverse event during period 1, notably epistaxis, madarosis and skin abscesses. Five deaths (5 of 44; 11.4%) occurred in the open-label period and, while considered unlikely to be related, causality cannot be ruled out. The primary efficacy end point in period 1 (total lesion activity by PET-CT) was not met (P = 0.0741). As the development of new HO lesions was suppressed in period 1, the primary efficacy end point in period 2 was prospectively changed to the number of new HO lesions versus period 1. No placebo patients crossing over to garetosmab developed new HO lesions (0% in period 2 versus 40.9% in period 1; P = 0.0027). Further investigation of garetosmab in FOP is ongoing. ClinicalTrials.gov identifier NCT03188666 .

Most Fractures Treated Nonoperatively in Individuals With Fibrodysplasia Ossificans Progressiva Heal With a Paucity of Flareups, Heterotopic Ossification, and Loss of Mobility.

BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) is an ultrarare genetic disorder with episodic and progressive heterotopic ossification. Tissue trauma is a major risk factor for flareups, heterotopic ossification (HO), and loss of mobility in patients with FOP. The International Clinical Council on FOP generally recommends avoiding surgery in patients with FOP unless the situation is life-threatening, because soft tissue injury can trigger an FOP flareup. Surprisingly little is known about flareups, HO formation, and loss of mobility after fractures of the normotopic (occurring in the normal place, distinct from heterotopic) skeleton when treated nonoperatively in patients with FOP. QUESTIONS/PURPOSES: (1) What proportion of fractures had radiographic evidence of union (defined as radiographic evidence of healing at 6 weeks) or nonunion (defined as the radiographic absence of a bridging callus at 3 years after the fracture)? (2) What proportion of patients had clinical symptoms of an FOP flareup because of the fracture (defined by increased pain or swelling at the fracture site within several days after closed immobilization)? (3) What proportion of patients with fractures had radiographic evidence of HO? (4) What proportion of patients lost movement after a fracture? METHODS: We retrospectively identified 36 patients with FOP from five continents who sustained 48 fractures of the normotopic skeleton from January 2001 to February 2021, who were treated nonoperatively, and who were followed for a minimum of 18 months after the fracture and for as long as 20 years, depending on when they sustained their fracture during the study period. Five patients (seven fractures) were excluded from the analysis to minimize cotreatment bias because these patients were enrolled in palovarotene clinical trials (NCT02190747 and NCT03312634) at the time of their fractures. Thus, we analyzed 31 patients (13 male, 18 female, median age 22 years, range 5 to 57 years) who sustained 41 fractures of the normotopic skeleton that were treated nonoperatively. Patients were analyzed at a median follow-up of 6 years (range 18 months to 20 years), and none was lost to follow-up. Clinical records for each patient were reviewed by the referring physician-author and the following data for each fracture were recorded: biological sex, ACVR1 gene pathogenic variant, age at the time of fracture, fracture mechanism, fracture location, initial treatment modality, prednisone use at the time of the fracture as indicated in the FOP Treatment Guidelines for flare prevention (2 mg/kg once daily for 4 days), patient-reported flareups (episodic inflammatory lesions of muscle and deep soft connective tissue characterized variably by swelling, escalating pain, stiffness, and immobility) after the fracture, follow-up radiographs of the fracture if available, HO formation (yes or no) as a result of the fracture determined at a minimum of 6 weeks after the fracture, and patient-reported loss of motion at least 6 months after and as long as 20 years after the fracture. Postfracture radiographs were available in 76% (31 of 41) of fractures in 25 patients and were independently reviewed by the referring physician-author and senior author for radiographic criteria of fracture healing and HO. RESULTS: Radiographic healing was noted in 97% (30 of 31) of fractures at 6 weeks after the incident fracture. Painless nonunion was noted in one patient who sustained a displaced patellar fracture and HO. In seven percent (three of 41) of fractures, patients reported increased pain or swelling at or near the fracture site within several days after fracture immobilization that likely indicated a site-specific FOP flareup. The same three patients reported a residual loss of motion 1 year after the fracture compared with their prefracture status. HO developed in 10% (three of 31) of the fractures for which follow-up radiographs were available. Patient-reported loss of motion occurred in 10% (four of 41) of fractures. Two of the four patients reported noticeable loss of motion and the other two patients reported that the joint was completely immobile (ankylosis). CONCLUSION: Most fractures treated nonoperatively in individuals with FOP healed with few flareups, little or no HO, and preservation of mobility, suggesting an uncoupling of fracture repair and HO, which are two inflammation-induced processes of endochondral ossification. These findings underscore the importance of considering nonoperative treatment for fractures in individuals with FOP. Physicians who treat fractures in patients with FOP should consult with a member of the International Clinical Council listed in the FOP Treatment Guidelines ( https://www.iccfop.org ). LEVEL OF EVIDENCE: Level IV, therapeutic study.

Vitamin D as a Nutri-Epigenetic Factor in Autoimmunity-A Review of Current Research and Reports on Vitamin D Deficiency in Autoimmune Diseases.

Epigenetics is a series of alterations regulating gene expression without disrupting the DNA sequence of bases. These regulatory mechanisms can result in embryogenesis, cellular differentiation, X-chromosome inactivation, and DNA-protein interactions. The main epigenetic mechanisms considered to play a major role in both health and disease are DNA methylation, histone modifications, and profiling of non-coding RNA. When the fragile balance between these simultaneously occurring phenomena is disrupted, the risk of pathology increases. Thus, the factors that determine proper epigenetic modeling are defined and those with disruptive influence are sought. Several such factors with proven negative effects have already been described. Diet and nutritional substances have recently been one of the most interesting targets of exploration for epigenetic modeling in disease states, including autoimmunity. The preventive role of proper nutrition and maintaining sufficient vitamin D concentration in maternal blood during pregnancy, as well as in the early years of life, is emphasized. Opportunities are also being investigated for affecting the course of the disease by exploring nutriepigenetics. The authors aim to review the literature presenting vitamin D as one of the important nutrients potentially modeling the course of disease in selected autoimmune disorders.

IL-17A, IL-17E and IL-17F as Potential Biomarkers for the Intensity of Low-Grade Inflammation and the Risk of Cardiovascular Diseases in Obese People.

Low-grade inflammation is a factor that predisposes to many obesity-related comorbidities. The immune mechanisms controlling the inflammatory response related to the secretory activity of adipocytes and its consequences for the organism are still under investigation. METHODS: 84 obese adult volunteers (BMI ≥ 30 kg/m2) were tested by BIA. Serum samples were collected to analyze the concentrations of interleukins IL-17A, IL-17E and IL-17F. The subjects completed the original questionnaire, the FFQ-6 food consumption frequency questionnaire and the food diary. RESULTS: The level of IL-17E and IL-17F was positively correlated with the BMI value and the level of IL-17E increased with the content of subcutaneous fat. Its increased blood concentration was also observed in individuals who declared that they were diagnosed with atherosclerosis and/or were taking beta-blockers. Products that were related with a low level of the above-mentioned interleukins were vegetables, groats, eggs, red meat, fast-food and alcohol. The level of these interleukins was positively correlated with the frequent consumption of confectionery and breakfast cereals. Nutrients that decreased the concentrations of IL-17 isoforms were potassium, iron, vitamins B6 and C, and folic acid. CONCLUSIONS: Both IL-17E and IL-17F may be closely related to the intensity of low-grade inflammation and be biomarkers of cardiovascular disease risk. Food products or the nutrients they contain may affect the levels of the above-mentioned interleukins as well as IL-17A.

LncCDH5-3:3 Regulates Apoptosis, Proliferation, and Aggressiveness in Human Lung Cancer Cells.

(1) Lung cancer (both small cell and non-small cell) is the leading cause of new deaths associated with cancers globally in men and women. Long noncoding RNAs (lncRNAs) are associated with tumorigenesis in different types of tumors, including lung cancer. Herein, we discuss: (1) An examination of the expression profile of lncCDH5-3:3 in non-small cell lung cancer (NSCLC), and an evaluation of its functional role in lung cancer development and progression using in vitro models; (2) A quantitative real-time polymerase chain reaction assay that confirms lncCDH5-3:3 expression in tumor samples resected from 20 NSCLC patients, and that shows its statistically higher expression levels at stage III NSCLC, compared to stages I and II. Moreover, knockout (KO) and overexpression, as well as molecular and biochemical techniques, were used to investigate the biological functions of lncCDH5-3:3 in NSCLC cells, with a focus on the cells' proliferation and migration; (3) The finding that lncCDH5-3:3 silencing promotes apoptosis and probably regulates the cell cycle and E-cadherin expression in adenocarcinoma cell lines. In comparison, lncCDH5-3:3 overexpression increases the expression levels of proliferation and epithelial-to-mesenchymal transition markers, such as EpCAM, Akt, and ERK1/2; however, at the same time, it also stimulates the expression of E-cadherin, which conversely inhibits the mobility capabilities of lung cancer cells; (4) The results of this study, which provide important insights into the role of lncRNAs in lung cancer. Our study shows that lncCDH5-3:3 affects important features of lung cancer cells, such as their viability and motility. The results support the idea that lncCDH5-3:3 is probably involved in the oncogenesis of NSCLC through the regulation of apoptosis and tumor cell metastasis formation.

MicroRNA gene methylation landscape in pediatric B-cell precursor acute lymphoblastic leukemia.

BACKGROUND: Aberrant DNA methylation is an important mechanism by which the normal patterns of microRNA expression are disrupted in human cancers including B-cell precursor acute lymphoblastic leukemia (BCP ALL), the most common pediatric malignancy. OBJECTIVES: To characterize the methylation profile landscape of microRNA genes in BCP ALL patients. MATERIAL AND METHODS: We employed Infinium® MethylationEPIC BeadChip Arrays to measure the methylation of microRNA genes from bone marrow samples of children with BCP ALL (n = 38) and controls without neoplasms (n = 4). RESULTS: This analysis revealed differential methylation of the microRNA genes in the pediatric BCP ALL when compared to the control. A subcluster amongst BCP ALL patients with TCF3-PBX1 genetic subtype was also observed. No other differences were observed in association with age, gender or risk group. Several interesting leukemia-related phenotypes are enriched by the genes with hyperand hypomethylated sites located in promoters as well as gene bodies. The top 3 miRNA genes, promoters of which were the most statistically significantly hypermethylated in BCP ALL were MIR1273G, MIR1304 and MIR663, and the top 3 hypomethylated were MIR4442, MIR155 and MIR3909. CONCLUSIONS: In this study, a different microRNA genes methylation landscape was shown in pediatric BCP ALL compared to children without neoplasms. A visible subcluster among BCP ALL samples consisted of individuals with TCF3-PBX1 genetic subtype. No other differences were observed in association with age, gender or risk group. Several interesting leukemia-connected phenotypes were found, associated with genes with hyperand hypomethylated sites located on promoters as well as gene bodies.

TiO2 - do we have to worry about it? One of the important aetiological factors in inflammatory bowel disease.

TiO2 in the food industry, designated as E171, is widely used in the production of chewing gums, sweets, and icing. It is absorbed through food ingestion and the respiratory tract. There are also reports that TiO2 nanoparticles can reach the dermis through damaged epidermis. It demonstrates the ability to accumulate in some internal organs, like spleen, liver, and kidneys, depending on its size and structure. It may have pro-inflammatory, cytotoxic, and genotoxic effects. A change in the composition of the host's intestinal microflora is also observed after exposure to high doses of TiO2. There are some differences in TiO2 intake with food around the world, but most data indicate higher consumption of this additive by children. Due to the small amount of research and the fact that most of the analyses were carried out using animal models, it is necessary to plan future observations of long-term exposure of the TiO2 molecule.

Dietary Intake of Endocrine Disrupting Substances Presents in Environment and Their Impact on Thyroid Function.

According to the available data, environmental pollution is a serious problem all over the world. Between 2015 and 2016, pollution was responsible for approximately nine million deaths worldwide. They also include endocrine disrupting chemicals (EDCs) that can interfere with the functioning of the thyroid gland. They are characterized by high persistence in the environment. These substances can enter the body through the gastrointestinal tract, respiratory system, as well as contact with the skin and overcome the placental barrier. EDC can be found in food, water, and personal care products. They can get into food from the environment and as a result of their migration to food products and cosmetics from packaging. EDCs can disrupt the functioning of the thyroid gland through a number of mechanisms, including disrupting the activation of thyroid receptors and the expression of genes that are related to the metabolism, synthesis, and transport of thyroid hormones (HT). There is a need to strengthen the food safety policy that aimed at the use of appropriate materials in direct contact with food. At the same time, an important action is to reduce the production of all waste and, when possible, use biodegradable packaging, which may contribute to the improvement of the quality of the entire ecosystem and the health of food, thus reducing the risk of developing thyroid diseases.

Potential Immunomodulatory Effects from Consumption of Nutrients in Whole Foods and Supplements on the Frequency and Course of Infection: Preliminary Results.

A diet rich in nutrients should be implemented in order to boost the immune system and prevent infections. To investigate which nutrients are commonly consumed, an anonymous survey was given to 120 individuals and their responses were collected. The respondents answered questions relating to their health status, and their consumption of nutrients and supplements that produce immunomodulating effects. The participants were also asked about any prior viral, bacterial or fungal infections experienced, and in particular, infection frequency, course, and duration. The data collected were subjected to a statistical analyses to assess the relationship between the reported frequency of infections and nutrients consumed including vitamins D3, A, C, E, selenium, zinc, iron, ß-carotene, omega-3 fatty acids as well as live active probiotic bacteria. The findings show that vitamin and mineral supplementation did not positively affect the duration, frequency, or course of infections in the surveyed sample. An exception was vitamin D3 supplementation that was correlated to sporadic incidence of viral infections. Conversely, immunity was positively affected by consumption of natural nutrients contained in whole food (vitamin C, iron, selenium, omega-3 fatty acids), evidenced by lower incidences and milder courses of infection.

Pyoderma Gangrenosum with an Underlying Leukocyte Adhesion Deficiency Type 1 (LAD-1) and Pregnancy in the Shade of COVID-19 Epidemic: A Patient and Physician Experience.

In the first part of this article, the anonymous patient diagnosed with leukocyte adhesion deficiency type 1 (LAD-1) and pyoderma gangrenosum (PG) discusses her experience of her medical history and treatment in a foreign country during her pregnancy and the coronavirus disease-19 (COVID-19) pandemic. The patient's dermatologists, immunologist, and diagnostician refer to the epidemiology, genetics, diagnosis, morphologic manifestations, including skin lesions, treatment, and prognosis in LAD-1. The patient's diagnostic and therapeutic process was discussed in the last part of this paper.

Effect of interleukin-6, -17, -21, -22, and -23 and STAT3 on signal transduction pathways and their inhibition in autoimmune arthritis.

Rheumatic diseases are complex autoimmune diseases which include among others rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), and psoriatic arthritis (PsA). These diseases are characterized by prolonged and increased secretion of inflammatory factors, eventually leading to inflammation. This is often accompanied by persistent pain and stiffness in the joint and finally bone destruction and osteoporosis. These diseases can occur at any age, regardless of gender or origin. Autoimmune arthritis is admittedly associated with long-term treatment, and discontinuation of medication is associated with unavoidable relapse. Therefore, it is important to detect the disease at an early stage and apply appropriate preventative measures. During inflammation, pro-inflammatory factors such as interleukins (IL)-6, -17, -21, -22, and -23 are secreted, while anti-inflammatory factors including IL-10 are downregulated. Research conducted over the past several years has focused on inhibiting inflammatory pathways and activating anti-inflammatory factors to improve the quality of life of people with rheumatic diseases. The aim of this paper is to review current knowledge on stimulatory and inhibitory pathways involving the signal transducer and activator of transcription 3 (STAT3). STAT3 has been shown to be one of the crucial factors involved in inflammation and is directly linked with other pro-inflammatory factors and thus is a target of current research on rheumatoid diseases.

Evaluation of Selected Parameters of the Specific Immune Response against Pseudomonas aeruginosa Strains.

The immune response to Pseudomonas aeruginosa strains could be influenced by differences in antibiotic resistance and virulence. At the present time, it is unclear which type of immune responses enables uncontrolled invasion of opportunistic pathogens. The conditional pathogenicity of Pseudomonas aeruginosa served as an inspiration to begin a study on this bacterium. The aim of this study was to gain insight into selected parameters describing immune responses with regards to the adaptable agents of this pathogen. For the analysis of the specific immune response, the potential of Pseudomonas aeruginosa to stimulate lymphocytes, including Th17 lymphocytes, dendritic cells and other components of the adaptive immune response, was examined. The highest percentage of CD83+CD1a-HLA-DR++ cells was found after stimulation with lysates of strains isolated from the patients with severe systemic infection. We found statistically significant differences in percentages of HLA-DR+ PBMCs and MFI of HLA-DR between groups of Pseudomonas aeruginosa strains isolated from the patients with different clinical courses of infection. Our results suggest that the clinical course and outcomes of Pseudomonas aeruginosa infections are not associated with impairment of the specific immune response.

Coincidence of selective immunoglobulin A deficiency in juvenile idiopathic arthritis - a series of three cases.

Immunoglobulin A (IgA) deficiency is the most common primary immunodeficiency in humans, with incidence depending on ethnic background and the highest frequency in Caucasians. Selective IgA deficiency may have an asymptomatic course and constitute a random laboratory finding with no clinical manifestation. There is, however, a group of patients with increased incidence of recurrent upper respiratory tract infections, allergies, asthma, atopic dermatitis and other pathologies connected with IgA deficiency. This group of patients often needs broad-spectrum antibiotic therapy with maximum doses and extended time of treatment as there is no causal treatment for IgA deficiency. An association between IgA deficiency and autoimmune diseases, such as juvenile idiopathic arthritis, has been proved before. Nonetheless, the frequency of co-occurrence of these disorders in an individual as well as the way immunodeficiency may influence the course of juvenile idiopathic arthritis is still undefined, with limited literature on this topic. This article presents case reports of three pediatric patients with confirmed co-occurrence of IgA deficiency and oligoarticular juvenile idiopathic arthritis.

An association of iNKT+/CD3+/CD161+ lymphocytes in ovarian cancer tissue with CA125 serum concentration.

The purpose of this study was to investigate the association of iNKT (human invariant natural killer T) cells with the key marker of ovarian cancer (OC) - CA125 (cancer antigen125) in serum. The study reports the assessment of iNKT cells in peripheral blood and tissue of benign and borderline ovarian tumors (BOTs) and in the advanced-stage ovarian cancer. The study groups were as follows: 25 women with benign ovarian tumors, 11 women with BOTs, and 24 women with primary advanced-stage ovarian cancers. The control group consisted of 20 patients without the ovarian pathology. The rates of iNKT lymphocytes in the peripheral blood and tissue specimens were evaluated by a flow cytometry. Significant differences in the percentage of iNKT+/CD3+ of CD3+ lymphocytes, iNKT+/CD3+/CD161+ among CD3+ and iNKT+/CD3+/CD161+ among CD3+/iNKT+ between the control group and patients with ovarian tumors in the peripheral blood and tumor tissue were identified. Significant correlations were noticed between the proportion of lymphocytes iNKT+/CD3+/CD161+ among CD3+/iNKT cells in blood and in cancer tissue of both benign and malignant tumors. In the OC group, neither the ratio of iNKT cells in the blood (P = 0.07), nor the intra-tumor NKT-cell infiltration (P = 0.5) were independent prognostic factors for the follow-up. An increased rate of iNKT cells was detected in benign ovarian tumors compared to OCs. In patients with ovarian cancer, a higher rate of iNKT cells in tumor tissue was present related to that noted in the patient's blood. In addition, a correlation was discovered between the CA125 serum marker and NKT cells from the ovarian cancer tissue. This article has for the first time demonstrated a negative relationship between serum levels and NKT lymphocyte count from ovarian tissue. The inflammatory process in ovarian cancer tissue and the potential infiltration of endothelial immune cells, may result in a reduced number of NKT cells in the tumor microenvironment and increased circulation of the CA125 marker. Presented findings underscore new aspects of the iNKT cells involvement in the ovarian cancer development.