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In addition to identifying the major B- and T-cell subpopulations involved in autoimmune rheumatic diseases (ARDs), in recent years special attention has been paid to studying the expression of their activation markers and immune checkpoints (ICPs). The activation markers on B and T cells are a consequence of the immune response, and these molecules are considered as sensitive specific markers of ARD activity and as promising targets for immunotherapy. ICPs regulate the activation of the immune response by preventing the initiation of autoimmune processes, and they modulate it by reducing immune cell-induced organ and tissue damage. The article considers the possible correlation of ICPs with the activity of ARDs, the efficacy of specific ARD treatments, and the prospects for the use of activation molecules and activation/blocking ICPs for the treatment of ARDs.

Introduction. Natural killer T lymphocytes (NKT) take place between the innate and acquired immune response. The ability of these cells to activate the antitumor immune response and inhibit immunological activity makes them the target of research in cancer patients. The radicality of surgical treatment of patients with metastatic melanoma (stage III–IV) is relatively conventional. In this regard, the possibility of adjuvant effective therapy of melanoma is actively investigated worldwide.The aim of the study is investigation of the importance of increasing the number of NKT cells in the peripheral blood of patients with metastatic melanoma after radical surgical removal of the tumor. Patients were treated with adjuvant regimen antitumor autologous dendritic cell therapy in form of vaccination.Materials and methods. The study included 39 patients with stage III and IV metastatic melanoma with regional and / or distant metastases after radical surgery. From the peripheral blood monocytes of each patient, an autologous vaccine was created from mature dendritic cells loaded with tumor lysate. The therapy continued until objective progression. The study included patients who received from 5 to 120 injections. The follow-up period ranged from 5 to 168 months.Results. It was shown that 14 (36 %) of patients had the number of NKT cells exceeding the norm (0–10 %) and in the course of vaccine therapy they had the progression of the disease in the period up to 2 years. In patients with relapse-free course of the disease in vaccine therapy (n = 13), the number of NKT lymphocytes did not exceed the norm both before and during therapy. Significantly shorter time to progression was revealed in patients with high initial content of NKT lymphocytes compared with patients with normal indices of NKT cells (6.5 months) – 95 % confidence limit 2,4–10,7 % vs 96,2 months (95 % confidence limit 63.8–128.6 %). Conclusion. An increased number of NKT cells in patients with stage III–IV metastatic melanoma after radical surgical treatment is a marker of early progression.

Introduction. Age is considered as an important clinical and pathological factor in cancer patients. Malignant tumors are more likely to develop in older people, but the disease is less aggressive than in young patients. According to various authors, the influence of age on the development of tumors largely depends on the age-related features of the immune system.The aim of the present study was to determine the relationship of indicators of systemic antitumor immune response with the age of patients with primary operable breast cancer and cancer of the oral mucosa.Materials and methods. The study included patients with all subtypes of primary-operable breast cancer (n = 145) and patients with cancer of the oral mucosa (n = 29). Immunophenotyping of peripheral blood lymphocytes was performed using a wide panel of monoclonal antibodies to markers of adaptive and innate immunity cells.Results. In elder patients (40 years and older) with primary-operable breast cancer, the percentage of activated CD25+ lymphocytes and CD4+CD25+ and CD3+CD4+ T cells, NKT cells, activated HLA-DR+ lymphocytes, including activated CD3+HLA-DR+ T cells before treatment, was statistically significantly higher than in patients younger than 40 years. Patients of this group showed increase of CD8+CD - 11b+CD28– CTLs and a decrease in the number of naive lymphocytes (CD4 – CD62L+ and CD8+CD11b – CD28+) in comparison with control percentage, and the downward trend in CD4+CD25+CD127– Treg, with increased numbers of CD4+CD25+ T cells. In patients with cancer of the oral mucosa, an increase in the number of cells of some populations of the immune effector link and a decrease in the number of suppressor lymphocytes were revealed with age.Conclusion. The results suggest that age-related differences in the state of systemic antitumor immune response contribute to a more favorable course of breast cancer and some other malignancies in older persons. It is obvious that the features of age differences in the immune response to the tumor should be taken into account when prescribing systemic therapy, including immunotherapy.All patients gave written informed consent to participate in the study

Introduction. Long-term monitoring of immune system parameters in cancer patient in FSBI “N.N. Blokhin Medical Research Center of Oncology” of the Ministry of Health of Russia, as well as the absence of an immunological research algorithm and a spectrum of significant markers, served as the basis for this study.Purpose. To present reference values and determine the normal range for subpopulations of systemic immunity lymphocytes.Materials and methods. The phenotype of peripheral blood lymphocytes was studied in 186 healthy donors (86 men and 100 women), mean age 41,9 ± 12,5 years. To assess the multivariate phenotype by flow cytometry, monoclonal antibodies to CD45, CD3, CD4, CD8, CD16, CD56, CD19, CD25, CD28, CD11b, CD127, HLA-Dr, TCR-γ / δ, Perforin and Granzime B labeled various fluorochromes.Results. A panel of markers of immunocompetent cells of systemic immunity was developed as a basis for assessing the state of the immune system of cancer patients. Reference values and normal boundaries are given for characterizing the linearity of cells with detailing of the phenotypic and functional heterogeneity of the population of CD8+-lymphocytes, activation markers and the pool of naive cells; characteristics of various types of regulatory cells, functional activity of cells of the effector link of immunity. A comparative analysis of immunoregulatory indices was carried out and the vulnerability of the formula CD3+CD4+/CD3+CD8+ to the CD4+/CD8+ index was proved.Conclusion. The spectrum of the proposed indicators is the product of many years of research carried out in the laboratory of clinical immunology of the Federal State Budgetary Institution “N.N. Blokhin National Medical Research Center of Oncology” оf the Ministry of Health of the Russian Federation, in order to search for significant criteria for assessing the state of the immune system in cancer.