In solid tumors, tumor-associated macrophages (TAMs) are one of the most numerous populations and play an important role in the processes of tumor cell invasion, metastasis, and angiogenesis. Therefore, TAMs are considered promising diagnostic and prognostic biomarkers of tumors, and many attempts have been made to influence these cells as part of antitumor therapy. There are several key principles of action on ТАМs: the inhibition of monocyte/macrophage transition; the destruction of macrophages; the reprogramming of macrophage phenotypes (polarization of M2 macrophages to M1); the stimulation of phagocytic activity of macrophages and CAR-M therapy. Despite the large number of studies in this area, to date, there are no adequate approaches using antitumor therapy based on alterations in TAM functioning that would show high efficacy when administered in a mono-regimen for the treatment of malignant neoplasms. Studies devoted to the evaluation of the efficacy of drugs acting on TAMs are characterized by a small sample and the large heterogeneity of patient groups; in addition, in such studies, chemotherapy or immunotherapy is used, which significantly complicates the evaluation of the effectiveness of the agent acting on TAMs. In this review, we attempted to systematize the evidence on attempts to influence TAMs in malignancies such as lung cancer, breast cancer, colorectal cancer, cervical cancer, prostate cancer, gastric cancer, head and neck squamous cell cancer, and soft tissue sarcomas.

The international consensus Sepsis-3 in 2016 defined sepsis as life-threatening organ dysfunction caused by a disruption of the host response to infection. One of the main mechanisms leading to the death of patients with sepsis is an imbalance of the immune response to pathogens. Activation of immune cells, in particular neutrophils, plays a key role in the mechanisms of sepsis. During sepsis, the number of immature neutrophils in the blood increases, PD-L1 neutrophils appear, which have an immunosuppressive function, and the number of Neu1 subtype of neutrophils, characterized by high expression of the NF-kB inhibitor, the chemokine CXCL8, olfactomedine, which regulates the production of cytokines, and myeloperoxidase, increases. When the inflammatory response generalizes, the phagocytic and bactericidal functions of neutrophils are disrupted. An important role in the mechanisms of sepsis is played by the formation of neutrophil extracellular traps, extracellular DNA, and the nuclear non-histone protein HMGB1, which are DAMPs and have proinflammatory activity. The development of approaches to predicting the development and course of sepsis in injuries and infectious and inflammatory diseases based on assessing the functional activity of neutrophils and their phenotype is a promising area of research, in particular approaches to regulating the functioning of neutrophils using miRNA.

Background: the general lifespan has been prolonged greatly during the past century, and the incidence of age-associated diseases, including neurodegenerative ones, has increased as well. However, modelling of age-related pathologies is mostly conducted on adult rodents. We studied morphofunctional changes in the brain and peripheral blood of adult Wistar rats in comparison with old Wistar rats to determine age-related physiological changes and differences in adaptive reactions to AlCl₃ exposure. Methods: the work was performed on adult and old male Wistar rats. The animals consumed a 100 mg/kg solution of AlCl₃ each day for 60 days. Morphological changes of neurons and microglia, mRNA expression levels of pro-inflammatory and anti-inflammatory cytokines, microglia activation markers, amyloid-related proteins, and hallmarks of cellular senescence, monocyte, and lymphocyte subpopulations in the peripheral blood were examined. Results: old rats showed increasing hyperchromic neurons in the hippocampus; activation of microglia; upregulation of pro-inflammatory cytokines and cellular senescence markers; downregulation of anti-inflammatory cytokines; and Hif-1a and a decrease in B-cells and monocyte in peripheral blood. Conclusion: compared to young animals, aged rats respond to aluminum exposure with a severe decline of most cells’ function and irreversible neuronal loss. Regarding all reported data, neurodegeneration modelling and investigating of factors capable of accelerating or preventing it should be performed in experimental work on aged animals.

The search for markers applicable for efficient differential diagnosis and personalized therapy is a priority task of experimental neuro-oncology. Modern molecular methods allow us to analyze human biopsy material; however, further actions with this extracted tumor tissue are limited. Relevant and sophisticated CNS tumor models are required for precise therapy development. Although it is possible to use human biomaterial to create 2D and 3D cultures and implant them into xenograft animals, the data generated from such models is limited. Due to changes in the classification of the CNS tumors in 2021, a representative model should have not only morphological similarity to human tumors but also key genetic aberrations for studying the mechanisms of carcinogenesis and personalized therapy (such as PDGFRa, Olig1/2, Sox2, and Mki67) for different glioma models such as astrocytoma, oligodendroglioma, and glioblastoma. On the basis of a unique scientific facility “The Collection of experimental tumors of the nervous system and neural tumor cell lines” (Avtsyn Research Institute of Human Morphology of “Petrovsky National Research Center of Surgery”), there is a biobank of chemically induced transplantable tumors of laboratory animals. Their properties, mechanisms, and progression closely correlate with malignant CNS neoplasms in humans. These are potentially useful for identifying novel signaling pathways associated with oncogenesis in the nervous system and personalizing therapeutic approaches. In our work, we characterized a tissue-transplantable brain tumor strain of rat glioma101.8 using MRI, IHC, scRNA-seq, and qPCR-RT methods. According to this study, the cellular composition of the tissue-transplantable rat glioma 101.8 strain was determined, as well as the major genetic signature characteristics of each cell population of this tissue-transplantable strain and its microenvironment.

Glioblastoma (GBM) is a highly aggressive human neoplasm with poor prognosis due to its malignancy and therapy resistance. To evaluate the efficacy of antitumor therapy, cell models are used most widely, but they are not as relevant to human GBMs as tissue models of gliomas, closely corresponding to human GBMs in cell heterogeneity. In this work, we compared three different tissue strains of rat GBM 101.8 (induced by DMBA), GBM 11-9-2, and GBM 14-4-5 (induced by ENU). Materials and methods: We estimated different gene expressions by qPCR-RT and conducted Western blotting and histological and morphometric analysis of three different tissue strains of rat GBM. Results: GBM 101.8 was characterized by the shortest period of tumor growth and the greatest number of necroses and mitoses; overexpression of Abcb1, Sox2, Cdkn2a, Cyclin D, and Trp53; and downregulated expression of Vegfa, Pdgfra, and Pten; as well as a high level of HIF-1α protein content. GBM 11-9-2 and GBM 14-4-5 were relevant to low-grade gliomas and characterized by downregulated Mgmt expression; furthermore, a low content of CD133 protein was found in GBM 11-9-2. Conclusions: GBM 101.8 is a reliable model for further investigation due to its similarity to high-grade human GBMs, while GBM 11-9-2 and GBM 14-4-5 correspond to Grade 2–3 gliomas.

The impact of histological subtype on immunogenic properties of the tumor microenvironment in synovial sarcomas (SSs) remains understudied. This study aimed to conduct a comparative assessment of tumor microenvironments in monophasic and biphasic SSs. During the study, biomaterial from nine patients with SS was analyzed using IHC analysis, flow cytometry, and real-time PCR. All tumors were infiltrated with CD45+ leukocytes, including the diffusely scattered CD68+ macrophages. FAP+ cells were identified in 7/9 observations, including both monophasic and biphasic tumors. CD4+ T cells and CD20+ B cells were identified by IHC in biphasic SS. The flow cytometry assay revealed significantly higher counts of CD4+ and CD8+ lymphocytes in biphasic SS. IHC revealed E-cadherin expression specifically in the epithelial component of biphasic SS. Vimentin expression in the mesenchymal component of biphasic SS was stronger than in monophasic tumors. The reverse transcription real-time PCR assay revealed higher expression of tumor markers CDKN2A, EGFR, and PDGFRL in monophasic SS. Expression levels of M2 macrophage marker ARG1 and levels of M1 macrophage marker NOS2 in monophasic SS were higher than in biphasic tumors. Biphasic and monophasic SSs revealed distinct molecular patterns and differential degrees of T lymphocyte and M2 macrophage infiltration. Biphasic SSs are characterized by the presence of lymphocytes in the tumor, while monophasic SSs show more pronounced infiltration with M2 macrophages. Monophasic tumors are characterized by higher expression of cancer-related genes CDKN2A, EGFR, and PDGFRL, which can be considered as potential targets for treatment. Our study is limited to a small sample of patients. This is due to the rarity of synovial sarcoma, as well as the fact that we recruited patients who had not received radiation or chemotherapy before taking the biomaterial. It was these criteria that made it possible to objectively assess the state of the tumor microenvironment.