The review presents analysis of the papers that discuss mechanisms of antitumor immunity. The role of innate and adaptive immune reactions as well as local and systemic is considered in terms of immune defense in clinical and experimental studies. The article discusses characteristics and role tumor-associated antigens for clinical practice. Various types of immune effector cells, including T-cells, NK-cell, DC, tumor associated macrophages, etc., and cytokines, are discussed regarding their contribution into antitumor immune response. The authors also refer to the hypothesis of “immunoediting” and its part in antitumor immunity.

ФГБНУ «Научно-исследовательский институт вакцин и сывороток им. И.И. Мечникова», Москва 2 ГБОУ ВПО «Пермский государственный медицинский университет имени академика Е.А. Вагнера» Минздрава России 3 ФГБНУ «Российский онкологический научный центр им. Н.Н. Блохина», Москва Иммуногенная активность секретируемых белоксодержащих соединений Staphylococcus aureus № 6 Резюме Трудность терапии инфекций, вызываемых S. aureus, определяется резистентностью возбудителя к применяемым антибиотикам, хроническим характером течения болезни, а также развитием на ее фоне снижения функций врожденного иммунитета и резистентности организма к инфекции. Несмотря на многочисленные усилия исследователей, в настоящее время отсутствуют противостафилококковые препараты, эффективность которых была бы установлена в завершенных клинических испытаниях. Цель работы: получение секретируемых белоксодержащих соединений S. aureus № 6 и изучение их иммуногенных свойств. Материалы и методы. Секретируемые белоксодержащие соединения (БСС) получали: «исходное»-из фильтратов культуральной жидкости S. aureus № 6, выращенных до конца фазы экспоненциального роста в соответствии с описанной ранее технологией I БСС и II БСС-после ионообменной хроматографии «исходного» БСС на колонках соответственно Q-Sepharose и dEAE-Sepharose. Накопление специфических IgG в сыворотках крови иммунизированных кроликов и мышей изучали в ИФА, иммуногенную активность-в опытах активной и пассивной защиты мышей линии BALB/с, по обсемененности органов и анализу формирования абсцессов в почках. Результаты. Изученные БСС обладали антигенной активностью (повышение в 2,2-7,5 раза уровня специфических IgG в сыворотках иммунизированных животных по сравнению с контролем), что свидетельствует об стимуляции системы адаптивного иммунитета и о существенной протективной активности: в опытах по активной (индекс эффективности 2,63-4,28) и пассивной защите. Иммунизация мышей «исходным» и II БСС значительно снижала высеваемость S. aureus из тканей почек мышей и формирование абсцессов в почках. Это свидетельствует о влиянии изучаемых БСС на тяжесть течения стафилококковой инфекции и позволяет предположить их терапевтическое действие. Заключение. Проведенный комплексный анализ выявил перспективность дальнейшего изучения «исходного» и II белоксодержащих соединений, имеющих высокий протективный потенциал в доклинических исследованиях, в качестве кандидатов на включение в состав препарата для иммунопрофилактики и иммунотерапии инфекций, вызываемых S. aureus.

Immune checkpoint inhibitors (ICT) therapy is a successful immunotherapy (IT) strategy that is quite effective in a number of patients with non-small cell lung cancer, melanoma, bladder cancer, breast cancer and others. Nevertheless, there is a need in predictive markers for ICT therapy for personalized IT as far as there is a large group of patients, the proportion of which varies depending on the tumor, who do not have a clinical response to such therapy. The review summarizes the theoretical aspects and results of clinical trials dedicated to various clinical efficiency predictor using modern databases. As a result of the analysis it is established that the main candidates for the role of such markers are tumor infiltrating lymphocytes and their subpopulations, peripheral blood lymphocytes (PBL) and their subpopulations. PD1 (programmed death receptor 1) and PDL1 (programmed death receptor ligand 1) expression in tumor tissue can also be important for predicting IT efficiency. The most promising predictive biomarker meaning the most clinically relevant is a combination of the PBL subpopulations study and PD1 and PDL1 expression on the tumor cells.PubMed, Scopus, Web of Science, eLibrary, Russian Science Citation Index databases were searched for the available appropriate literature reports. The authors included 82 in the given review.

In recent years, there is a persistent increase in the spread of community-acquired infections and medical care associated infections, the cause of which is S. aureus. Previously using liquid chromatography in combination with mass spectrometry (LC-MS) analysis, spectrum of having protective activity S. aureus № 6 proteins with a molecular weight of 30 - 50 kDa, secreted into the culture medium at the end of the exponential growth phase, was investigated. 11 proteins were identified from indicated peptides and preliminary results of the protective activity of the secreted protein-based substances (SPS), marked as «initial», were obtained. While its fractionation with ion exchange chromatography on DEAE-Sepharose, the protective fraction - II SPS - was obtained. Its hypodermic immunization leads to reduction of kidney inoculation, and to kidney abscess formation, compared to the control, during the generalized infection of mice BALB/c, developing as a result of retro-orbital injection of sublethal dose S. aureus. Aim. investigation the protective extracellular proteome II SPS S. aureus № 6. Material and methods. LC-MS analysis of the received data was carried out by comparing the detected mass-spectrum protein IISPS with the results of proteomic study of the virulent strain of S. aureus Newman widely used in researches. More than 100 interacting protein clusters were identified for certain using various databases. Results. During analysis main attention was paid to 46 identified proteins involved in various biological processes. Thus, the largest group (19 proteins) is composed of carbohydrate metabolism enzymes, eight of which are involved in key stages of glycolysis; 6 proteins are related to pathogenicity factors (including clamping factors A and B, gaptoglobin-adhesive surface protein) and 4 proteins are related to stress ones. The remaining 17 proteins represent a large group of proteins involved in various metabolic and biosynthetic processes. Conclusion. The received results confirmed the data of other researchers on the identification of a large number of secreted proteins of S. aureus and on their low coincidence with secreted from clinical isolates. This demonstrates the validity of the postulate of the plasticity of the S. aureus genome affecting the exoproteome profile that largely determines the difficulties in creation of effective anti-staphylococcal vaccines.

Purpose of research. To evaluate the effect of LAC (mononuclear blood leukocytes activated by IL-2 ex vivo) suspension infusion on clinical, biochemical, hematological and immunological characteristics of a healthy Beagle dog to assess the safety of the product’s application. Materials and methods. The research object is a 6-year Beagle dog male. The LAC suspension in Hank’s solution has been infused intravenously with a low rate of administration; the dose used was 25 m cells in 5 ml. An autologous culture of LAC has been generated from canine blood, evaluated by morphology, phenotype, and target activity in Laboratory of Cell Immunity by FBSI «N.N. Blokhin National Medical Research Center of Oncology». Results. The analysis of hematological, immunological and radiological characteristics of the object has identified no signs of any pathology development. That turns to conclusion that the given LAC medication dose’s local, hematological and systemic toxicity is low or absent. Conclusions. Data received within the research may be of interest to human medicine as well as to veterinary medicine as it could be considered a part of pre-clinical trials of the LAC suspension, which effectiveness has already been confirmed in human clinical oncology, and also as a safety assessment of even more complex constructs based on activated immunocompetent cells that are still under development. The study can serve as a basis for the development of activated leukocytes-based cellular anticancer immunotherapy (LAC, immune checkpoint molecules and SAR), primarily its toxicity studying models, and also be a part of pre-clinical studies of LAC toxicity.