The interaction of the innate and adaptive immunity is necessary for the immune response to SARS-CoV-2. The innate immunity serves as the body’s first line of defense in a rapid and non-specific manner. The adaptive immune reaction proceeds more slowly, forming a specific response to antigens. Both innate and adaptive immune responses are very important in the pathogenesis of COVID-19. Alterations in the immune status leading to impaired immune responses are associated with more serious infectious diseases, including COVID-19. Patients with cancer are often immunosuppressed, both as a result of their disease and the specific treatment. As a result, they are at a more serious risk of acquiring COVID-19.

The aim of the paper is to review the literature concerning the immune response to the coronavirus disease in cancer patients, particularly, those who received antitumor immunotherapy.

The review considers various retrospective and prospective studies evaluating the impact of SARS-CoV-2 infection on the effectiveness of treatment and the status of patients with cancer. The researchers have found that the negative impact of the infection affects patients receiving chemotherapy, patients with hematological malignancies, lung cancer, metastatic malignant neoplasms and cancer patients with advanced cancer. The age over 65 years is recognized as a certain risk factor.

Moreover, on the basis of the data on the mechanism of action of the immunotherapy with checkpoint inhibitors and the immune response to coronavirus infection, it was assumed that immune checkpoint inhibitors can induce immunocompetence in patients infected with SARS-CoV-2. However, the existing data cannot completely support the statement that the use of immune checkpoint inhibitors in cancer patients with COVID-19 causes increased mortality or morbidity with SARS-CoV-2 infection.

Extensive experimental and clinical studies are required to determine the role of cancer immunotherapy in COVID-19 patients with cancer.

Several types of COVID-19 vaccines have been developed in a short period of time. However, the groups at risk of severe COVID-19 (the elderly, people with suppressed immunity, such as oncological patients, or organ transplantation patients) are the least likely to develop an adequate immune response to vaccination. Therefore, in order to obtain protective reactions in these groups, it is advisable to use such biomedical cell products (BMCP) as dendritic cell (DC) based vaccines loaded with SARS-CoV-2 antigens ex vivo under optimal conditions. In some cases, when vaccination has not been carried out in a timely manner and the risk of a serious disease is high, it is worth-while to take immediate measures to protect the body from the virus that has infected the organism.

For this protective action lymphocytes with chimeric antigen receptors (CAR) may be suitable. Such receptors recognize antigens using modified antibody domains, without need for presentation within molecules of major histocompatibility complex. Therefore, it is possible to use donor effector CAR lymphocytes, which were prepared in advance, for emergency needs. CAR lymphocytes are currently used primarily for tumor therapy. Until 2020, there was limited research on antiviral CAR lymphocytes. However, the COVID-19 pandemic has led to a dramatic intensification of such activities. DCs, which are considered to be the most effective antigen-presenting cells, were also originally used as anti-tumor vaccines. The safety of DC vaccines, their high effectiveness in the presentation of target antigens quickly led researchers to try using DCs also as a therapeutic agent for chronic viral diseases such as hepatitis B and C, human immunodeficiecy virus.

This review summarizes the data on antiviral BMCPs that have been developed so far, with a particular focus on products against COVID-19. It discusses how the results of previous studies can be used to increase the efficiency of anti-COVID-19 BMCP.

Background. Cancer-testicular (CT) genes express in tumor cells in many cancers, including endometrial cancer (ER). CT genes mRNA was detected in the blood of patients with neoplasms, which determines the prospects of using CT gene mRNA as tumor-associated biomarkers. In the peripheral blood of patients with ER, the expression of CT genes has not been studied before.

Objective. Аssessment of occurrence of mRNA of the CT genes MAGEA1–MAGEA6 (MAGEA(1–6)), SSX1, 2, 4, XAGE1, MAGEC1, NY-ESO1 in the tumors and peripheral blood of patients with ER.

Materials and methods. The work used 52 samples of tumor and 54 samples of whole peripheral blood of patients 39–79 years old diagnosed with RE who were treated in clinics in Nizhny Novgorod, as well as the blood of 30 healthy volunteers. In blood and tumors, the frequency of occurrence of mRNA of 12 CT genes was determined using multiplex reverse transcription polymerase chain reaction.

Results. It has been shown that the mRNA of the tested CT genes is detected in ER not only in tumors, but also in the peripheral blood of patients. The most common mRNA is MAGEA(1–6). At the same time, both in tumors and in the peripheral blood of patients, high heterogeneity in the expression of CT genes detected. Moreover, cases of MAGEA(1–6), SSX1, 2, 4, XAGE1, NY-ESO1, MAGEC1 mRNA detection in tumors were revealed in the absence of their detection in the peripheral blood and conversely. The total frequency of MAGEA(1–6), SSX1, 2, 4, XAGE1, NY-ESO1, MAGEC1 mRNA occurrence in tumors was 75.0 %, and in peripheral blood – 44.6 %. As in tumors, most blood samples showed expression of only one CT gene. Only in some cases the expression of two or three genes was recorded. Note that in all blood samples of healthy volunteers mRNA CT genes was not detected. Additionally, mixed form of macroscopic growth (both exophytic and endophytic), growth along the uterine fundus and walls, as well as low degree of differentiation were followed by a higher mRNA CT genes occurrence in the blood and tumors.

Conclusion. In ER mRNA CT genes occur in the blood and tumors of patients. A more severe course of ER is associated with an increase in the incidence of mRNA CT genes.

Backgrоund. Breast cancer molecular subtypes serve as a basis for combined treatment of the disease. Some of them (e. g. triple negative subtype) are prognostically unfavorable. Recently, we’ve demonstrated role of bone marrow B-cells in breast cancer prognosis. Correlation between these parameters (molecular subtypes and bone marrow lymphocyte subpopulations) have not yet studied.

Aim. To investigate prognostic role of breast cancer molecular subtypes and to see the relationships between these subtypes and subpopulational composition of bone marrow lymphocytes.

Materials and methods. Detailed study of bone marrow has been performed in all 107 patients treated in breast cancer department of N.N. Blokhin National Medical Research Center of Oncology in 2013–2016 years. Distribution of patients according to molecular subtypes were as follows: Luminal A – 36 (33.6 %) pts, Luminal B HER2-negative – 38 (35.5 %), Luminal B HER2-positive – 15 (14 %), subtype with Erb-B2 hyper-expression – 5 (4.4 %), triple negative – 13 (12.1 %). Comparison of molecular subtypes with immunological parameters was done for the following bone marrow B-lymphocyte subpopulations: CD19⁺, CD19⁺CD10⁺, CD19⁺CD38⁺, CD19⁺CD5⁺. The following survival data were analyzed: overall survival, relapse-free survival, progression-free survival, metastasis-free survival.

Results. Breast cancer molecular subtypes were not related to overall survival of patients but influenced relapse-free survival, progression-free survival and metastasis-free survival. There were no correlation between molecular subtypes and bone marrow B-lymphocyte subpopulations CD19, CD19⁺CD10⁺, CD19⁺CD38⁺. B1-lymphocytes were related to molecular subtypes, the levels of B1 cells were significantly higher in Erb-B2 subtype compared to triple-negative subtype (p = 0.039).

Conclusion. Breast cancer molecular subtypes are different in prognosis – relapse-free survival, progression-free survival and metastasis-free survival. The most prognostically unfavorable is triple-negative subtype. There are some relationships of bone marrow subpopulations and molecular subtypes of breast cancer: levels of B1-cells are much higher in Erb-B2 subtype compared to triple negative subtype (p = 0.039).

Background. The incidence of oral mucosa cancer (OMC) is higher in people over 50 years of age, and the aggressiveness of the course of the disease is higher in people under 50 years of age. In this context, it is of interest to clarify the mechanisms of immune disorders characteristic of patients of different age groups.

Aim. To research systemic and local immunity in OMC patients and the relationship of peripheral blood lymphocyte population (PBLs) and tumor infiltrating lymphocytes (TILs) with the patient’s sex and age.

Materials and methods. PBLs and TILs effector and suppressor populations were studied by flow cytometry in OMC patients aged 29 to 84 years.

Results. The percentage of CD3^-, CD3⁺CD4⁺ and CD3⁺CD8⁺T cells, regulatory CD4⁺CD25⁺CD127^{low/ –}(CD4Treg) and CD8⁺CD11b^–CD28^–(CD8Тreg) T lymphocytes, CD4⁺PD-1⁺ and CD8⁺PD-1⁺ T cells was increased in TILs compared to PBLs. The levels of cytotoxic CD8⁺CD11b⁺CD28^– T lymphocytes, NK, CD8⁺Perforin⁺ and CD16⁺Perforin⁺ cells in TILs were lower than in PBLs. The relationship between the level of CD4Treg and other TILs and PBLs depended on the patient’s sex. Age-related changes in the levels of NK and CD8 T-cells were observed in men, and CD4Treg – in women.

Conclusion. Local immunity in OMC patients is highly immunosuppressive. The sex of patients influences the relationship between CD4Treg and other populations of PBLs and TILs, as well as age-related changes in the OMC patients’ immune system. This investigation results can make a certain contribution to personalized treatment of patients with OMC, taking into account differences in systemic and local immunity and in the immune response to the tumor in patients of different sex and age.

Background. Molecules of the major histocompatibility complex in cancer are currently being widely studied, and their clinical significance is still the subject of controversy. It is reported that they might have an important predictive value in the effectiveness of immunotherapy. The study of the expression HLA molecules status in breast cancer provides a deeper understanding of the biological properties of the tumor, in particular to identify the features of its immunological phenotype, which may further influence on breast cancer therapy.

Aim. To evaluate the frequency of HLA-immunophenotypes in breast cancer and their relationship with the clinical and morphological features of the primary tumor.

Materials and methods. This study included 82 patients with breast cancer who received treatment at the N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia. Immunophenotyping of the primary tumor was performed by immunofluorescence on cryostat sections. The reaction was evaluated using a ZEISS Axioscope 5 luminescent microscope (Zeiss AG, Germany). The study was dominated by patients with stage IIB 54 %, stage IIA was detected in 5 % of cases, IIIA – in 12 % of cases, IIIB – in 21 % of cases, IIIC – 8 %. Infiltrative ductal breast cancer was diagnosed in 67 % of patients (n = 55), infiltrative-lobular – in 22 % of cases (n = 18), other types – in 11 % (n = 9). The frequency of immunophenotypes was studied depending on the clinical and morphological characteristics of breast cancer.

Results. It was found that in the group as a whole, the HLA-binegative immunophenotype of breast cancer was predominant. It dominated at stage T4 compared to the HLA-I⁺/HLA-DR⁺ phenotype (100 and 0 %), p = 0.042. At the same time, it should be noted that in T4 primary tumor the HLA-I⁺/HLA-DR^– immunophenotype was also observed. The relationship this immunophenotype was noted with the stage: frequency at stage IIIA was higher than the HLA-I⁺/HLA-DR⁺ phenotype, 60 and 40 %, p = 0.01. Both HLA-DR-negative immunophenotypes were characterized by a high incidence of lymph node involvement and the absence of estrogen receptor expression. 80 % of receptor-negative tumors were noted in HLA-binegative immunophenotype compared to phenotype HLA-I⁺/HLA-DR⁺, p = 0.022; the similar data were obtained for the HLA-I⁺/HLA-DR^– immunophenotype (p = 0.037).

Conclusion. HLA immunophenotypes analysis of breast cancer revealed the HLA-binegative immunophenotype of breast cancer was predominant. The second most common immunophenotype was the absence of expression of HLA-DR molecules. The association of HLA-immunophenotypes with the stage of the tumor process, the size of the primary tumor, and the expression status of estrogen receptors was revealed.

Background. Radiation therapy is one of the main treatments for locally advanced cancers of the rectum, cervix, and prostate. As a result of summing up high total doses, radiation damage occurs in patients.

Aim. To determine the frequency of late radiation injuries in patients, their impact on overall survival and quality of life.

Materials and methods. The study included 759 patients who received treatment in medical facilities in St. Petersburg and the Leningrad Region, of which 324 were men and 435 were women aged 27–88 years, with a diagnosis of rectal cancer – 257, cervical cancer – 327, prostate cancer – 175 patients. Irradiation was carried out on linear accelerators and brachytherapy devices. The quality of life of patients was assessed by questionnaires based on QLQ-30.

Results. The overall toxicity was 35.01 % in patients with cervical cancer, 10.4 % in patients with rectal cancer and 7.6 % in patients with prostate cancer. Overall long-term 5 and 10 years survival in patients with late complications was 46.3 and 16.5 % versus 66.5 and 33.4 % in patients without late complications (p = 0.001). In patients diagnosed with rectal cancer, it was significantly higher than in other groups (p <0.05). 3–5 weeks after the end of radiation therapy, patients reported a significant deterioration in the quality of life.

Conclusion. Late radiation damage is an important prognostic factor influencing long-term survival in patients diagnosed with cancer of the rectum, cervix and prostate. A decrease in the quality of life in patients who received irradiation of the pelvic organs 3–5 weeks after the end of radiation therapy has been proven.

Background. Solid tumors can create their aggressive properties. There are characterized by the invasion and metastatic activity, the resistance of the tumor clone to apoptosis. These pathways triggering may be realized both by 2-deoxy-D-ribose and its phosphorylated form (2-d-D-Rib-1-P), and by hydrogen peroxide.

Aim. To investigate the peculiarities of enzymes activity to nucleoside metabolism and antioxidant system in epithelial tumors of different localization.

Materials and methods. The features of the thymidine phosphorylase, adenosine deaminase, superoxide dismutase (SOD) and glutathione peroxidase (GPO) activity were studied in tumor homogenates. The visually no transformed tissues of the surgical resection edges were used as a control. Enzymes activity was determined by spectrophotometrical and morphological features were examined by the immunohistochemical methods in tissues of non-small cell lung cancer (NSCLC), samples of gastric and colon carcinomas (GCC).

Results. Thymidine phosphorylase activity and adenosine deaminase activity in various malignant tumors were increased in comparison to the control. Respectively, thymidine phosphorylase activity was higher than by 1.8 times (p = 0.002 for NSCLC, p = 0.001 for GCC). An increase of adenosine deaminase activity was revealed both in tissues of NSCLC (more than 1.7 times) and in GCC (by 1.9 times, p = 0.001). No significant changes in SOD activity were detected in the tumors. GPO activity tended to decrease by an average of 1.3 times (p = 0.01 for NSCLC, p = 0.02 for GCC). A cluster analysis of the enzymatic activity features of the studied NSCLC tumors, as well as GCC, revealed their metabolic heterogeneity. According to its results, tumors of different localization were distinguished into 2 clusters. Common feature to their second clusters was an increase the SOD activity. It was accompanied by increase of thymidine phosphorylase activity (p = 0.045 for NSCLC, p = 0.049 for GCC). Therefore, both hydrogen peroxide and 2-d-D-Rib-1-P could be formed in them more intensively. It is important to note that morphological indicators of tumor aggression (decreased or lost expression of cell-cell adhesion marker, expression of mesenchymal markers, active angiogenesis) were detected more frequently in these subgroups.

Conclusion. The obtained results reveal that individual features of the enzymes activity in epithelial tumors may be available source of 2-d-D-Rib-1-P and hydrogen peroxide generation in human cancer cells. In the case of individual higher tumor activity of thymidine phosphorylase and SOD and low GPO activity the metabolic stimulation of tumor progression may be occur.