Vol 22, No 1 (2025)

Many recent studies have focused on regulatory T cells (Tregs). These cells crucial to maintain immune tolerance and regulate the immune response to autoantigens, allergens, pathogens, and tumors. Epigenetic changes can provide a relatively stable pattern of Treg gene expression, producing suppressor cytokines such as interleukin-10 (IL-10), transforming growth factor beta (TGF-β), and IL-35, as well as inhibitory molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), lymphocyte activation gene 3 (LAG-3), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), cluster of differentiation 73 (CD73), and CD39. However, Tregs are a flexible and evolving cell population that depends on epigenetic factors and the microenvironment. Prolonged antigen stimulation during chronic infections causes T cell exhaustion, leading to the loss of effector function and decreased secretion of interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and IL-2, as well as to the development of suppressor potential. Under certain conditions, the expression of the transcription factor Forkhead box P3 (Foxp3) decreases in Tregs, leading to the loss of suppressor activity and cell differentiation into memory T cells, which can maintain chronic inflammation. Infectious pathogens often stimulate Treg activity, which reduces the immune response and can potentially trigger autoimmune diseases. Tregs prevent inflammation and immune disorders by functioning in various non-lymphoid tissues. In addition, they can perform non-traditional functions in non-lymphoid organs associated with tissue development and homeostasis maintenance. Extracellular vesicles secreted by Tregs play an important role in both protective and pathogenic activities. These vesicles contain molecules that target recipient cells and regulate their function. Therefore, Tregs are involved in both the suppression and induction of acute and chronic immune inflammation. For this reason, current research need to be focused on developing new approaches to diagnose and treat autoimmune, infectious, and tumor diseases.

Azoximer bromide is an immunomodulator. Despite its long-term use and evidence of its potential antitumor activity, the role of azoximer bromide in oncology is still unclear. We conducted a systematic review to evaluate the available evidence on how azoximer bromide affects the typical safety outcomes of anticancer treatments.

The review included papers published from 2000 to 2022 from the Cochrane, eLibrary.Ru, and PubMed databases, as well as relevant publications from their references. The inclusion criteria were confirmed cancer and evidenсe on antitumor efficacy (objective response and survival rates), immunological efficacy (effects on immune system parameters), and safety of azoximer bromide in combination with standard treatment options or as monotherapy. Owning to of the high level of data heterogeneity, only a descriptive analysis and a publication quality assessment were performed.

The review included 16 studies. The azoximer bromide treatment regimens showed a high level of heterogeneity. The use of azoximer bromide was associated with an increase in certain T-lymphocyte subpopulations and a shift in the ratio of T-helpers (Th) and cytotoxic T-lymphocytes toward CD4⁺ cells. The azoximer bromide groups showed a significant decrease in the rate of adverse events compared with the control groups. Patients who received azoximer bromide were found to have a higher overall survival rate, longer time to progression, and longer duration of response. However, the included studies had a low level of evidence.

The analysis shows that it is necessary and feasible to evaluate azoximer bromide in randomized trials as part of combined cancer therapy.

Background: Some current evidence suggest that myeloperoxidase may participate in the pathogenesis of atherosclerosis. However, its role in the development of unstable atherosclerotic lesions in humans and effects on a collagen-elastin scaffold of the vascular wall are poorly understood.

Aim: This study aimed to compare the immunohistochemical assays of myeloperoxidase, smooth muscle cells, and elastic and collagen fibers in various types of human atherosclerotic lesions.

Methods: Histology and immunohistochemistry tests were performed on autopsy samples obtained from 21 patients who died from acute cardiovascular failure caused by atherosclerosis. Segments of the aorta (from the arch, thoracic, and abdominal regions), coronary arteries, and the basilar artery were examined. A total of 50 tissue samples were included. We used a highly sensitive, two-step avidin–biotin assay technique to detect myeloperoxidase expression in various types of atherosclerotic vascular wall lesions.

Results: Intracellular myeloperoxidase location was detected in the intima of unstable atherosclerotic plaques, and its amount increased as the lesions progressed. However, unstable plaques showed a significant decrease in smooth muscle cells and destruction of the collagen–elastin scaffold. This was accompanied by the degradation of elastic and collagen fibers, as well as the rupture of the plaque cap.

Conclusion: It is hypothesized that the production of myeloperoxidase by mononuclear cells negatively affects human smooth muscle cells by promoting apoptosis and inhibiting the synthesis of elastic and collagen fibers in the vascular wall. This may destabilize atherosclerotic lesions.