The Melanoma-Associated Antigen Family A (MAGE-A): A Promising Target for Cancer Immunotherapy?

Early efforts to identify tumor-associated antigens over the last decade have provided unique cancer epitopes for targeted cancer therapy. MAGE-A proteins are a subclass of cancer/testis (CT) antigens that are presented on the cell surface by MHC class I molecules as an immune-privileged site. This is due to their restricted expression to germline cells and a wide range of cancers, where they are associated with resistance to chemotherapy, metastasis, and cancer cells with an increasing potential for survival.

Influence of Cucurbiturils on the Production of Reactive Oxygen Species by T- and B-Lymphocytes, Platelets and Red Blood Cells.

Reactive oxygen species (ROS) are highly reactive chemical molecules containing oxygen. ROS play an important role in signaling and cell homeostasis at low and moderate concentrations. ROS could be a cause of damage to proteins, nucleic acids, lipids, membranes and organelles at high concentrations.

The Influence of Severity and Disease Duration on TNF Receptors' Redistribution in Asthma and Rheumatoid Arthritis.

One of the mechanisms of cellular dysfunction during the chronization of immune-system-mediated inflammatory diseases is a change in the profile of expression and co-expression of receptors on cells. The aim of this study was to compare patterns of redistribution of TNF receptors (TNFRs) among patients with different durations of rheumatoid arthritis (RA) or asthma. Subgroup analysis was performed on RA ( = 41) and asthma ( = 22) patients with disease duration<10 years and >10 years and on 30 comparable healthy individuals.

The role of metabolism on regulatory T cell development and its impact in tumor and transplantation immunity.

Regulatory CD4 T (Treg) cells play a key role in the induction of immune tolerance and in the prevention of autoimmune diseases. Treg cells are defined by the expression of transcription factor FOXP3, which ensures proliferation and induction of the suppressor activity of this cell population. In a tumor microenvironment, after transplantation or during autoimmune diseases, Treg cells can respond to various signals from their environment and this property ensures their suppressor function.

The Role of Tumor-Associated Antigen HER2/neu in Tumor Development and the Different Approaches for Using It in Treatment: Many Choices and Future Directions.

The treatment of HER2-positive cancers has changed significantly over the past ten years thanks to a significant number of promising new approaches that have been added to our arsenal in the fight against cancer, including monoclonal antibodies, inhibitors of tyrosine kinase, antibody-drug conjugates, vaccination, and particularly, adoptive-T-cell therapy after its great success in hematological malignancies. Equally important is the new methodology for determining patients eligible for targeted HER2 therapy, which has doubled the number of patients who can benefit from these treatments. However, despite the initial enthusiasm, there are still several problems in this field represented by drug resistance and tumor recurrence that require the further development of new more efficient drugs.

Integral Algorithms to Evaluate TiO and N-TiO Thin Films' Cytocompatibility.

Titanium oxide (TiO) and oxynitride (N-TiO) coatings can increase nitinol stents' cytocompatibility with endothelial cells. Methods of TiO and N-TiO sputtering and cytocompatibility assessments vary significantly among different research groups, making it difficult to compare results. The aim of this work was to develop an integral cytocompatibility index (ICI) and a decision tree algorithm (DTA) using the "EA.

Immune Transcriptome Study of Human Nucleated Erythroid Cells from Different Tissues by Single-Cell RNA-Sequencing.

Nucleated erythroid cells (NECs) are the precursors of erythrocytes. They can be found in various hematopoietic tissues or in the blood. Recently, they have been shown to be active players in immunosuppression through the synthesis of arginase-2 and reactive oxygen species.

Dendritic cells transfected with a polyepitope DNA construct stimulate an antitumor cytotoxic response in various tumors.

Dendritic cells (DCs) loaded with tumor-associated antigens (TAAs) are known to be crucial for the antitumor response and are still included in various treatment regimens in cancer immunotherapy research. In the present study, a cell-based protocol was evaluated, involving the use of original DNA constructs encoding the wide range of TAA epitopes expressed on different epithelial cancers. The constructs were transfected into -generated DCs of patients with various types of cancer, including breast, colorectal and non-small cell lung cancer.

Delayed effects of neonatal immune activation on brain neurochemistry and hypothalamic-pituitary-adrenal axis functioning.

During the postnatal period, the brain is highly sensitive to stress and inflammation, which are hazardous to normal growth and development. There is increasing evidence that inflammatory processes in the early postnatal period increase the risk of psychopathologies and cognitive impairment later in life. On the other hand, there are few studies on the ability of infectious agents to cause long-term neuroinflammation, leading to changes in the hypothalamic-pituitary-adrenal axis functioning and an imbalance in the neurotransmitter system.

Immune Transcriptome and Secretome Differ between Human CD71+ Erythroid Cells from Adult Bone Marrow and Fetal Liver Parenchyma.

CD71+ erythroid cells (CECs) were only known as erythrocyte progenitors not so long ago. In present times, however, they have been shown to be active players in immune regulation, especially in immunosuppression by the means of ROS, arginase-1 and arginase-2 production. Here, we uncover organ-of-origin differences in cytokine gene expression using NanoString and protein production using Bio-Plex between CECs from healthy human adult bone marrow and from human fetal liver parenchyma.

Human Fetal Liver Parenchyma CD71+ Cells Have AIRE and Tissue-Specific Antigen Gene Expression.

Autoimmune regulator (AIRE) is a multifunctional protein that is capable of inducing tissue-specific antigens' (TSAs) gene expression, a key event in the induction of self-tolerance, that is usually expressed and functions in the thymus. However, its expression has been detected outside the thymus and cells expressing the gene have been named extra-thymic expressing cells (eTACs). Here, we discuss the finding of and TSAs gene expression in CD71+ cells from human fetal liver parenchyma, which are mostly represented by CD71+ erythroid cells.

Structural and functional characteristics of the hippocampus in depressive-like recipients after transplantation of in vitro caffeine-modulated immune cells.

The hippocampus is a key anatomical brain region associated with depression. On the other hand, immune cells and their releasing cytokines play an essential role in stress and depression. Noteworthy that the most of psychoactive drugs produce unidirectional effects on the cells of both nervous and immune systems.

Model of Suppression of the Alloantigen Response by Tolerogenic Dendritic Cells Transfected with Personalized DNA Constructs Encoding HLA Epitopes.

Background: A search for efficient graft rejection modulation techniques for the promotion of durable engraftment remains to be a matter of close study all over the world. Despite the variety of immunosuppressive drugs, the schemes currently used show a lack of selectivity and have a number of side effects. Here we investigated an approach for the induction of antigen-specific tolerance in a human "stimulator-responder" model , using dendritic cells (DCs) transfected with designed DNA constructs encoding the stimulator's major histocompatibility complex (MHC) epitopes.

Redistribution of TNF Receptor 1 and 2 Expression on Immune Cells in Patients with Bronchial Asthma.

Background: The co-expression patterns of type 1 and 2 tumor necrosis factor (TNF)-α membrane receptors (TNFR1/TNFR2) are associated with the presence, stage, and activity of allergic diseases. The aim of this study was to assess the expression levels and dynamics of TNFRs on immune cells and to assess associations between their expression and severity of bronchial asthma (BA).

Methods: Patients with severe (n = 8), moderate (n = 10), and mild (n = 4) BA were enrolled.

Autoantibodies to Tumor Necrosis Factor in Patients with Active Pulmonary Tuberculosis.

Background: Tumor necrosis factor (TNF) plays an important role in immune responses to the causative agent of tuberculosis, . Additionally, TNF can also mediate many negative disease manifestations. The aim of this study was to assess the contribution of anti-TNF autoantibodies to the pathogenesis of active pulmonary tuberculosis (TB).

Observed efficacy and clinically important improvements in participants with osteoarthritis treated with subcutaneous tanezumab: results from a 56-week randomized NSAID-controlled study.

Background: A recent phase 3 study demonstrated that treatment with tanezumab, a nerve growth factor inhibitor, or nonsteroidal anti-inflammatory drugs (NSAIDs) improves pain and physical function in participants with moderate-to-severe osteoarthritis (OA) of the hip or knee. Here, we evaluated the time course and clinical importance of these initial efficacy findings using a mixture of primary, secondary, and post hoc endpoints.

Methods: Participants on stable NSAID therapy and with a history of inadequate response to other standard OA analgesics were enrolled in an 80-week (56-week treatment/24-week safety follow-up), randomized, NSAID-controlled, phase 3 study primarily designed to assess the safety of tanezumab for moderate-to-severe OA of the knee or hip.

Ligand-Regulated Expression of TNF Receptors 1 and 2 Determines Receptor-Mediated Functional Responses.

Introduction: Modulating specific biological effects through the changes in cytokine receptors' expression level remains poorly understood. This study aimed to investigate the influence of the dose-dependent effect of TNF on the balance between proapoptotic and proliferation response depending on the parameters of TNFR1/2 expression density.

Methods: Tumor cell lines (HEp-2, K-562, MCF-7, ZR-75/1, MOLT-4, IM-9, and Raji) were characterized for TNFR1/2 co-expression using flow cytometry and were studied to reveal the dose-dependent effect of rhTNF on cell cycle and apoptosis parameters.

Dietary Fucose Affects Macrophage Polarization and Reproductive Performance in Mice.

Intestinal mucus protects epithelial and immune cells from the gut resident microorganisms, and provides growth-promoting factors as mucus-derived O-glycans for beneficial bacteria. A lack of intestinal protective mucus results in changes in the commensal microflora composition, mucosal immune system reprogramming, and inflammation. Previous work has shown that fucose, the terminal glycan chain component of the intestinal glycoprotein Mucin2, and fucoidan polysaccharides have an anti-inflammatory effect in some mouse models of colitis.

T-regulatory cells from patients with rheumatoid arthritis retain suppressor functions .

Rheumatoid arthritis (RA) is a chronic disease of connective tissue caused by intolerance to self-antigens. Regulatory T cells (Tregs) are key players in maintaining autotolerance through a variety of suppressor mechanisms. RA is generally believed to develop due to disorders in Tregs; however, there is no consensus on this issue.

Tofacitinib as monotherapy following methotrexate withdrawal in patients with psoriatic arthritis previously treated with open-label tofacitinib plus methotrexate: a randomised, placebo-controlled substudy of OPAL Balance.

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis, rheumatoid arthritis, and ulcerative colitis. This study evaluated the efficacy and safety of tofacitinib 5 mg twice daily monotherapy after methotrexate withdrawal.

Methods: OPAL Balance was an open-label, long-term extension study of tofacitinib in patients with psoriatic arthritis who participated in the OPAL Broaden and OPAL Beyond phase 3 studies.

Dendritic Cells Transfected with MHC Antigenic Determinants of CBA Mice Induce Antigen-Specific Tolerance in C57Bl/6 Mice.

Background: Nonspecific immunosuppressive therapy for graft rejection and graft-versus-host disease (GVHD) is often accompanied by severe side effects such as opportunistic infections and cancers. Several approaches have been developed to suppress transplantation reactions using tolerogenic cells, including induction of FoxP3 Tregs with antigen-loaded dendritic cells (DCs) and induction of CD4IL-10 cells with interleukin IL-10-producing DCs. Here, we assessed the effectiveness of both approaches in the suppression of graft rejection and GVHD.

Primary Immunodeficiencies in Russia: Data From the National Registry.

Primary immunodeficiencies (PID) are a group of rare genetic disorders with a multitude of clinical symptoms. Characterization of epidemiological and clinical data via national registries has proven to be a valuable tool of studying these diseases. The Russian PID registry was set up in 2017, by the National Association of Experts in PID (NAEPID).

Tear cytokines as potential biomarkers in non-infectious uveitis: post hoc analysis of a randomised clinical trial.

Purpose: The study aimed to evaluate cytokines in tears as potential biomarkers in non-infectious uveitis.

Methods: Tear samples were obtained using Schirmer strips from 50 patients enrolled in a randomised controlled study of simvastatin in non-infectious uveitis and from a control group of 30 healthy participants. The concentrations of IL-6, IL-8, IL-10, and IFN-γ in tears were measured at the study's baseline and again after 8 weeks of treatment using commercial enzyme-linked immunosorbent assay kits.

Co-Expression of Membrane-Bound Tumor Necrosis Factor-Alpha Receptor Types 1 and 2 by Tumor Cell Lines.

Introduction: Density and co-expression of tumor necrosis factor (TNF) receptors may vary among cell populations. However, the role and potential of these changes remain unclear. This study aimed to determine the density of expression and co-expression of TNFR1/2 and the dose-dependent effect of soluble TNF on these parameters.

Co-Expression Profile of TNF Membrane-Bound Receptors Type 1 and 2 in Rheumatoid Arthritis on Immunocompetent Cells Subsets.

Introduction: Tumor necrosis factor (TNFα) is an important proinflammatory cytokine in rheumatoid arthritis (RA) immune processes. However, TNFα activity and functions may be regulated by soluble receptors, which act as decoys, and by number, density, and co-expression of its membrane-bound receptors type 1 and 2 (TNFR1 and TNFR2). The aim of this study was to reveal associations between TNFR1/2 co-expression profile parameters and RA disease activity indicators.