It is known that the immune system plays one of the main roles in the development of oncology. This is confirmed by the fact that patients with congenital or acquired immunodeficiency have a higher risk of developing cancer. To date, there are several types of immunotherapy, each of which has its own mechanism of action. This review presents data from clinical studies of the main treatment options using immunotherapy mechanisms, such as cellular immunotherapy, the use of antibodies and cytokines, and combination immunotherapy (using checkpoint inhibitors). These data indicate a positive trend of this method of treatment in patients with cancer.

High-grade gliomas are aggressive brain tumors with limited survival rates. To date the maximum of survival benefit of conventional therapeutic options has been already reached and innovative treatment strategies, based on tumor biology are urgently needed. Generally, malignant gliomas, including glioblastoma, are immunologically “cold: neoplasms, with weak anti-tumor immune response and peritumoral inflammation, caused by reduced expression of neoantigens by tumor cells and restricted immunoreactivity of the microenvironment. The reduced immunogenicity of brain structures is conditioned by the absence of homing molecules for white blood cells on them, as well as the suppression of activated (CD178+) T cells by brain gangliosides. The cell population infiltrating malignant glioma is impoverished with cytotoxic T cells (CD8+ FOXP3–) and oppositely enriched with regulatory T cells and type 2 macrophages (M2). An effective anti-glioma immune response is resulted in increasing the total number of tumor-infiltrating lymphocytes and the CD8+ cell content; switching the functional activity of macrophages from M2 to M1 type. Integration of immunotherapeutic technologies (vaccines and monoclonal antibodies) into treatment strategies of malignant gliomas is relevant and promising approach based on biological features of the tumor.

Gliomas are the most common primary tumors of the central nervous system. Their aggressive form – glioblastomas is characterized by an unfavorable prognosis and a high frequency of relapses. It is believed that prior traumatic brain injury is one of the possible factors for the subsequent development of glial brain tumors. Several authors have proposed several criteria for establishing a possible causal relationship between traumatic brain injury and gliomas. However, the actual role of antecedent brain injury in the pathogenesis of this tumor type is still a matter of debate. It has been suggested that traumatic injuries cause an active and prolonged inflammatory process, while disrupting the permeability of the blood-brain barrier, which leads to exposure of the brain tissue to carcinogenic (toxic) substances, various growth factors or cells of the immune system circulating in the bloodstream, which ultimately can lead to malignant transformation of glial cells. One of the evidence for this hypothesis is supported by reports of meningiomas located adjacent to posttraumatic meninges and cerebral scars. In this paper, we will try to elucidate the potential relationship between traumatic brain injury and the formation of glial brain tumors.

Genomic instability caused by activated retroelements plays an important role in the development of malignant neoplasms. Activated retroelements cause enhanced expression of oncogenes containing transposon sequences in their promoters and introns. Oncosuppressor genes contain hot spots of insertional mutagenesis, therefore retroelements cause their inactivation. As a result, genomic instability increases during the development of tumors, since oncosuppressors normally silence retrotransposons. Accordingly, inactivation of the oncosuppressor causes increased expression of retroelements.

The study objective is to describe the role of retrotransposons on the development of hereditary tumor syndromes, which will allow a new look at the classical concepts of carcinogenesis. The data we have described allow us to consider in a new way the Knudson’s two-hit hypothesis in hereditary tumor syndromes, since the germinal inactivation of 1 allele of the oncosuppressor gene promotes the development of malignant tumors due to an increase in the activity of transposons. The consequence of the developed instability in the tumor is the inactivation of the second allele of the oncosuppressor gene, which contributes to clonal evolution and the progression of carcinogenesis.

Introduction. Hypermethylated CpG islands in the promoters of suppressor genes (in particular, SEPT9) are clinically significant markers of malignant growth that are widely used in liquid biopsy. Real-time polymerase chain reaction with methylation-specific primers is commonly used to quantify hypermethylated DNA. The method requires data normalization, depends on copy number variability of the calibrator genes, and is rather laborious.

The study subject is to develop an alternative qDMA method (quantitative DNA Melting Analysis).

Materials and methods. DNA samples isolated from blood plasma of healthy donors and colorectal cancer patients were analyzed by the method including: 1) asymmetric polymerase chain reaction with methylation-independent individually selected primers for the SEPT9 gene; 2) using the TaqMan probe hybridizing to two CpG dinucleotides in the amplicon; 3) post-amplification melting of probe/amplicon hybrids; 4) quantitative analysis of DNA melting.

Results. The method was tested on the SEPT9 gene in liquid biopsy of colorectal cancer. Differences in SEPT9 methylation in healthy donors (n = 41) and cancer patients (n = 39) were statistically significant (p <0.0001). Analytical sensitivity and diagnostic efficiency of qDMA were determined: AUC (area under curve) ROC– 0.812 (according to the result of 10-fold cross-validation AUC ROC – 0.801), sensitivity – 90%, specificity – 66%.

Conclusion. The proposed method for the quantitative assessment of aberrantly methylated DNA is simple, implemented in the closed-tube format, does not require normalization and usage of standard curves. The possibility of optimization through the use of a multiplex variant with simultaneous analysis of several markers is assumed.

The study objective is to analyze the prognostic significance of PRAME protein expression in patients with uveal melanoma using immunohistochemical assay.

Materials and methods. A total of 30 patients with uveal melanoma were examined and treated. The average age of patients at the time of treatment was 51.3 ± 11.8 years. In all cases, enucleation was performed according to the indications. A routine clinical-morphological, molecular-genetic, and immunohistochemical assay study was performed (n = 29). The immunohistochemical study was performed using antibodies to PRAME (clone 6H8, dilution 1: 50). The median follow-up period was 86.3 ± 2.9 months.

Results. Of the 29 samples studied, staining was determined in 16, which was 55.2 %. Weak intensity of 1+ staining (from 10 to 20 % of tumor cells) was detected in 7 uveal melanoma samples, medium intensity of 2+ (from 10 to 20 % of tumor cells) – also in 7, and strong intensity of 3+ (30 % of tumor cells) – in 2 tumor samples. When assessing the seven-year survival, the cumulative survival rate in the group without PRAME expression was 0.857, while in the group with PRAME expression it was significantly lower and amounted to 0.357 (p = 0.0001). The PRAME protein expression was significantly correlated with the epithelioid cell type of the tumor (p = 0.041) and with the total and partial monosomy of chromosome 3 (p = 0.013).

Conclusion. This paper presents the world’s first study of the prognostic significance of PRAME protein expression by immunohistochemical analysis in patients with uveal melanoma. A significant association of PRAME-positive patients with an unfavorable vital prognosis was shown.

Introduction. Non-small cell lung cancer is a common cancer with a poor prognosis. Modern researchers conduct many studies devoted to understanding the molecular mechanisms of its pathogenesis. Modern advances in immunotherapy have significantly improved the prognosis of patients with this pathology, but this is still not enough to control the course of the disease.

Objective – to the study of tumor (Ki-67, tumor necrosis factor α (TNF-α)) and stromal (TNF-α, CD20 and CD31) markers in non-small cell lung cancer and their prognostic significance.

Materials and methods. The study included tumor samples obtained from 100 patients with non-small cell lung cancer. The expression of Ki-67, TNF-α, CD20 and CD31 was assessed by immunohistochemistry. Survival analysis was carried out by constructing survival curves using the Kaplan–Meier method. To analyze the association of the expression of studied markers with clinical and morphological characteristics, the Mann–Whitney test was used. Differences were considered statistically significant at p <0.05.

Results. We analyzed the expression of Ki-67, TNF-α, CD20 and CD31 in non-small cell lung cancer tumors. Ki-67 expression was detected in tumor cells in 99 % of the samples studied and was not observed in stromal cells. In tumor and stromal cells, TNF-α expression was detected in 100 % of the samples. CD31 positive cells were also found in all samples studied, and CD20+B cells were present in 95 % of cases. TNF-α expression in tumor cells and tumor stroma is not associated with clinical and morphological characteristics. For the expression of CD20 in the tumor stroma, there was an association with tumor localization (p = 0.0435), with the stage of the disease (p = 0.0044), tumor size (p = 0.0017), and the presence of regional metastases (p = 0.0071). For Ki-67, there was a strong association with the histological type of tumor (p <0.0001), its localization (p = 0.0012) and the presence of regional metastases (p = 0.0020). The analysis of prognostic significance showed that TNF-α expression in tumor stroma cells is a favorable prognostic factor (hazard ratio 0.5547; p = 0.0139), while a high content of CD31+ cells is a factor of poor prognosis (hazard ratio 2.335; p = 0.0355). Next, we carried out a comprehensive analysis of the prognostic significance of the two identified markers simultaneously. It turned out that their combination of TNF-α/stroma (high expression)+CD31 (low expression) is a much more significant prognostic factor, in contrast to the individual analysis (hazard ratio 0.1966; p = 0.0048).

Conclusion. The study showed that a complex rather than an individual assessment of the predictive value of several markers simultaneously more effectively reflects their predictive ability.

Introduction. To a large extent, the resistance of glioblastoma multiforme to genotoxic therapy is associated with a dysregulation of responses to DNA damage and repair. Thus, suppression of DNA repair mechanisms is a priority pathway for increasing the survival rate of glioblastoma multiforme patients. Curcumin enhances the effectiveness of standard chemotherapy drugs, but its effect on DNA repair systems is not well understood.

The study objective – to study the molecular mechanisms of curcumin action on excisional DNA repair in U251 glioblastoma multiforme cells.

Materials and methods. high-resolution proteomic mass spectrometry, cell technologies.

Results. In the proteomes of two types of glioblastoma multiforme cells (control and experiment), a total of 2757 proteins were identified, of which 39 % were differentially expressed. Significant changes have been found in many signaling cascades that play an important role in carcinogenesis.

Conclusion. Curcumin suppressed excisional DNA repair by decreasing the expression of determinants APEX1, MSH6, PARP1. PCNA, POLD1, POLE3, RFC2, RPA.

Introduction. Despite the significant progress in investigation of genetic susceptibility to cancers, there are still unclear questions in the field of molecular epidemiology. Numerous new data obtained using modern sequencing technologies require large case/control studies in different populations.

The study objective – to investigate the prevalence of BRCA1*c.5161C>T mutation in unselected breast, ovarian and prostate cancer patients from Bashkortostan.

Materials and methods. In the presented study, the prevalence of the BRCA1*c.5161C>T mutation was assessed in breast cancer, ovarian cancer and prostate cancer patients (n = 696). The study cohorts includes individuals of Tatar and Bashkir ethnic origin living in Bashkortostan Republic.

Results. The BRCA1 mutation c.5161C>T was detected in patients with breast cancer, ovarian cancer and prostate cancer in individuals of Tatar ethnic origin with a frequency of ~1,3 % (6/449), but not in Bashkirs. This mutation was also detected in two individuals of control group (2/700). We conclude that the contribution of the BRCA1 mutation c.5161C>T to hereditary breast, ovarian and prostate cancers, is likely to be small in Bashkortostan Republic.

Conclusion. Further research will be required to investigate whether this mutation also plays a role in other populations of Turkic origin.