THE MAIN PARAMETERS OF CELLULAR IMMUNITY IN PATIENTS WITH TRIPLE-NEGATIVE BREAST CANCER: RELATIONSHIP WITH EFFICIENCY OF CHEMOTHERAPY

Chemotherapy is among the primary methods of treating advanced breast cancer. It was shown that clinical efficacy of various chemotherapeutic agents in many cases depends not only on their direct cytostatic and/or cytotoxic effect upon tumor cells, but also on their ability to modulate phenotype of the tumor cells and to influence anti-tumor immune response. Initial state of the immune system and its response to treatment is crucial. Antitumor response involves cells of innate and adaptive immunity (NK, NKT, T cells). These populations are heterogeneous and contain, e.g., cells with antitumor activity and regulatory (suppressor) cells that suppress immune response and promote tumor progression. The aim of this work was to determine the relationship between the initial state of cellular immunity of patients suffering from locally advanced breast cancer with triple negative phenotype, and clinical effect of chemotherapy (cisplatin + doxorubicin/paclitaxel), and studying effects of the therapy upon subpopulation profiles of peripheral blood lymphocytes in the patients. We registered the terms of the disease progression as well as overall survival and progression-free survival. The disease progressed in 25 of 53 cases (47.2%) whereas 28 of 53 patients (52.8%) remained progression-free. The observation period was 35.5 months. Laboratory examination of the patients included immunophenotyping of peripheral blood lymphocytes and determination of NK cell cytotoxic activity before and after chemotherapy. Percentages of effectors and regulatory lymphocyte populations were determined. The results obtained showed that, for some lymphocyte subsets, the pre-treatment differences of cell percentage deviations from control were found between the progression-free groups and patients with progression of the disease. The differences in percentages of NKT cells and lymphocytes expressing CD25 activation marker proved to be most significant. Decreased number of NKT cells and activated CD25+ lymphocytes prior to chemotherapy was associated with increased probability of disease progression. Reduced percentage of NKT cells against control was observed in 56% of patients from the progression group (PD), and only 21.4% in the group free of disease progression (DF). [OR = 4.6 (95% CI 1.4 to 15.4)]. Percentage of CD25+ lymphocytes was decreased from 68.2% in the PD group, and 28.6% for DF patients [OR = 5.4 (95% CI 1.6-18.1)]. We studied relationships between the overall survival (OS) and percentage of perforin-containing NK, NKT, and T cells, and mean perforin fluorescence density (PFD) in these lymphocyte subsets in 26 of the 53 patients before treatment. A statistically significant positive correlation was revealed between OS and perforin PFD in all the three cell populations under study. Normalization of the parameters altered before treatment, and an increase of T cell numbers was observed in the disease-free patients

НОВЫЕ ВОЗМОЖНОСТИ РЕГУЛЯЦИИ ПРОТИВООПУХОЛЕВОГО ИММУННОГО ОТВЕТА

The tumor has different mechanisms capable of destroying the immunological protection. Population of regulatory cells, along with other factors provide “escape” of the tumor from immune surveillance. In our laboratory, we studied the features of quantitative changes of some subpopulations of peripheral blood lymphocytes in primary operable breast cancer (BC) and melanoma at different stages of tumor growth and in the process of tumor therapy. In 94.5% of patients with breast cancer were found to increase compared to the control amount of NKT-cells with the phenotype CD45+CD3+ CD16+CD56+, 78% increase in number of CD8+CD28– T-cells, and 20.5% increase in the number of patients Regulatory CD4+CD25+FOXP3+ T cells. Was found to depend on changes in the number of these cells from the stage of the disease. Patients with stage I and II disease there was a statistically significant increase in the percentage of CD8+CD28– T–cells and CD45+CD3+ CD16+CD56+ NKT-cells compared to the donor. At the same time in patients with stage III the number of cells of both populations declined and did not differ from the norm. Such dynamics of quantitative changes were typical for the main populations of effector cells antitumor immunity. In the evaluation of patients with disseminated melanoma was found that no increase in the number of cytotoxic CD45+CD8+CD11b+ T cells in the treatment dendritic cell vaccine (DCV) appears to be an indication to stop vaccine therapy, initially increased amount of CD3+CD8+CD16+. NKT-cells may serve as grounds for refusal of DCV. A brief description of the major co-receptor inhibitor of T-cells, and monoclonal antibodies that block the inhibitory molecule on immune and tumor cells in order to increase the efficiency of anti-tumor immune response. Encouraging clinical results have been obtained by using anti-CTLA-4 (ipilimumab), and anti-PD-1 (nivolumab) monoclonal antibodies.Опухоль обладает различными механизмами, способными разрушать иммунологическую защиту. Популяции регуляторных клеток наряду с другими факторами обеспечивают «ускользание» опухоли от иммунологического надзора. В нашей лаборатории было проведено изучение особенностей количественных изменений некоторых субпопуляций лимфоцитов периферической крови у первично-операбельных больных раком молочной железы (РМЖ) и диссеминированной меланомой на разных этапах опухолевого роста и в процессе противоопухолевой терапии. У 94,5% больных РМЖ было обнаружено повышение по сравнению с контролем количества NKT-клеток с фенотипом CD45+CD3+CD16+CD56+, у 78% повышение количества CD8+CD28- Т-клеток, и у 20,5% больных повышение количества регуляторных CD4+CD25+FOXP3+ Т-клеток. Выявлена зависимость изменений количества этих клеток от стадии заболевания: у пациенток с I и II стадиями заболевания отмечалось статистически значимое повышение процента CD8+CD28- Т-клеток и CD45+CD3+CD16+CD56+ NKT-клеток по сравнению с донорами. В то же время у пациенток с III стадией количество клеток обеих популяций снижалось и практически не отличалось от нормы. Подобная динамика количественных изменений была характерна и для основных популяций клеток-эффекторов противоопухолевого иммунитета. При обследовании больных диссеминированной меланомой было обнаружено, что отсутствие повышения количества цитотоксических CD45+CD8+CD11b+ Т-клеток в процессе лечения дендритноклеточной вакциной (ДКВ), по-видимому, является показанием к прекращению вакцинотерапии, а исходно повышенное количество CD3+CD8+CD16+ NKT-клеток может служить основанием для отказа от ДКВ. Приводится краткое описание основных ко-ингибиторных рецепторов Т-клеток и моноклональных антител, блокирующих ингибиторные молекулы на иммунокомпетентных и опухолевых клетках, с целью повышения эффективности противоопухолевого иммунного ответа. Обнадеживающие клинические результаты были получены при применении анти-CTLA-4 (ипилимумаб) и анти-PD-1 (ниволумаб) моноклональных антител

ВАКЦИНОТЕРАПИЯ НА ОСНОВЕ ДЕНДРИТНЫХ КЛЕТОК У БОЛЬНЫХ ПОЧЕЧНО-КЛЕТОЧНЫМ РАКОМ

Objective: to study the efficiency and tolerance of autologous vaccine therapy based on dendritic cells (DC) in patients with renal cell carcinoma (RCC) and to examine changes in immunological parameters and their association with the efficiency of the therapy. Subjects and methods. Twenty-nine patients with RCC received autologous vaccine therapy based on DC in 2002 to 2008. Therapy was performed in the induction mode in 16 patients before disease progression and in the adjuvant mode (8 vaccinations) in 13 patients after radical nephrectomy (grade III) or radical metastasectomy. Peripheral blood monocyte-derived DCs treated with autologous tumor lysate were used to prepare the vaccine. Results. In a group of 16 patients with distant metastases, partial regressions were recorded in 2 (12.5%) patients and long (> 6-month) stabilizations of a tumor process were observed in other 2 (12.5%) patients. The median time prior to progression was 3 (range 1.5-12) months. Thirteen patients on adjuvant treatment did not achieve the median time to progression: 4 patients showed no signs of disease progression ?12 to ?25 months after metastasectomy. Patients with a clinical effect (disease regression or long stabilization) showed a significant increase in the populations of CD3+CD8+ and CD3-CD16+ T lymphocytes (natural killers (NK) cells) after 3 vaccinations from 23.3 to 27.2% (p = 0.018) and from 15.17 to 20.3%, respectively (p = 0.03). Prior to vaccine therapy, the count of CD3+CD16+-NK cells was thrice greater in patients with the progressive disease than that in the donor group - 11.2 and 3.5%, respectively. The baseline count of CD4+CD25+ Т lymphocytes in patients with progressive disease was also significantly higher than that in patients with the clinical effect - 12.01 and 5.6%, respectively. Conclusion. In patients with RCC, DC-based vaccine therapy is able to induce a specific anti-tumor immune response that is transformed into the clinical effect in some cases. The baseline count of suppressor T lymphocyte (NKT and T-reg) populations may be a factor that predicts the efficiency of autologous DC-based vaccine therapy in patients with RCC. This immunotherapeutic approach merits further study, by defining the indications for its application in patients with RCC.Цель исследования - определить эффективность и переносимость аутологичной вакцинотерапии на основе дендритных клеток (ДК) у больных почечно-клеточным раком (ПКР). Изучить динамику иммунологических показателей и их связь с эффективностью лечения. Материалы и методы. В период с 2002 по 2008 г. 29 больных ПКР получили аутологичную вакцинотерапию на основе ДК. У 16 пациентов с наличием отдаленных метастазов терапия проведена в индукционном режиме до прогрессирования болезни и у 13 - в адъювантном режиме (8 вакцинаций) после выполнения радикальной нефрэктомии (III степени) или радикальной метастазэктомии. Для приготовления вакцины использовали культивированные из моноцитов периферической крови ДК, обработанные аутологичным опухолевым лизатом. Результаты. В группе из 16 больных с наличием отдаленных метастазов у 2 (12,5%) зафиксированы частичные регрессии, еще у 2 (12,5%) пациентов наблюдались длительные стабилизации опухолевого процесса (>6 мес). Медиана времени до прогрессирования составила 3 (1,5-12+) мес. У 13 больных, получавших адъювантное лечение, медиана времени до прогрессирования не достигнута: 4 пациента после метастазэктомии наблюдаются без признаков прогрессирования болезни от ?d12 до ?d25 мес У больных с клиническим эффектом (регрессия или длительная стабилизация болезни) наблюдалось достоверное увеличение популяции CD3+CD8+ и CD3-CD16+ (натуральные киллеры - НК) Т-лимфоцитов после 3 вакцинаций с 23,3 до 27,2% (р=0,018) и с 15,17 до 20,3% (р=0,03) соответственно. У больных с прогрессирующим течением заболевания число CD3+CD16+-НКT-лимфоцитов до начала вакцинотерапии в 3 раза превышало значение этого показателя в донорской группе - 11,2 и 3,5% соответственно. Исходное содержание CD4+CD25+-популяции Т-лимфоцитов у пациентов с прогрессированием болезни также было достоверно выше, чем у больных с клиническим эффектом - 12,01 и 5,6% соответственно. Выводы. Вакцинотерапия, проведенная на основе ДК, способна индуцировать специфический противоопухолевый иммунный ответ у больных ПКР, который в отдельных случаях трансформируется в клинический эффект. Исходное содержание супрессорных популяций Т-лимфоцитов (НКT и T-reg) может являться фактором, прогнозирующим эффективность проведения вакцинотерапии на основе аутологичных ДК у больных ПКР. Целесообразно дальнейшее изучение данного иммунотерапевтического подхода с определением показаний к его использованию у больных ПКР

Субпопуляционный состав опухоль-инфильтрирующих лимфоцитов при раннем и местнораспространенном тройном негативном раке молочной железы и его влияние на эффективность неоадъювантной химиотерапии

Recent studies have shown that triple-negative breast cancer (TN BC) is characterized by the highest mutational load and immunogenicity compared to other subtypes, as well as the degree of tumor-infiltrating lymphocytes (TILs) infiltration, which play an important role in the development of antitumor immunity and treatment response. A significant disadvantage of the standard immunohistochemical method for determining TILs is the inability to fully assess the subpopulation structure of the immune infiltration, including minor populations.Aim: The evaluation of the subpopulations of breast cancer lymphoid infiltration in patients receiving neoadjuvant chemotherapy (NACT) and its influence on achieving a complete pathomorphological response (pCR = RCB 0).Materials and methods: The study included 90 patients who received NACT in following regimen: AC (doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2) every 2 weeks, followed by 12 weekly infusions of paclitaxel 80 mg/m2 + carboplatin AUC2. The TILs subpopulations were evaluated in core-biopsy samples prior to the NACT in all patients. The analysis performed by flow cytofluorimetry. Clinical and immunological analysis was performed for the following 9 lymphocyte subpopulations: CD3+CD4+, CD3+CD8+, CD4+CD25highCD127– / low, CD3–CD19+, CD3–CD16+CD56+, CD3+CD16+CD56+, CD4+CD25+, CD8+CD279+, CD4+CD279+.Results: The frequency of pCR was 51,1 %. The total TILs content in groups with pCR and non-pCR (RCB 0 vs RCB I–III) did not differ statistically (p = 0.271). The subpopulations analysis for CD3+CD8+, CD3–CD16+CD56+, CD3+CD16+CD56+, CD3+CD4+, CD3–CD19+, CD4+CD25+, CD4+CD25highCD127– / low and CD4+CD279+ revealed no statistically significant differences between the median values in the groups with pCR and non-pCR. A study of the CD8+CD279+ population showed a higher level of these cells in patients achieved pCR / RCB 0 (median 18,6 % vs 12,3 % with RCB I–III) (p = 0.033). With CD8+CD279+ above the median (high, > Me), the pCR frequency was 61 % vs 35 % in the subgroup with CD8+CD279+ less than or equal to the median (low, ≤Me). Despite the absence of statistically significant differences in the content of CD3+CD16+CD56+(NKT-cells) in groups with pCR and non-pCR (p = 0.091), numerical differences in medians were revealed: 9,9 % and 8,3 %, respectively. At the same time, with CD3+CD16+CD56+(NKT) > Me (high), the pCR frequency was 63 % vs 36 % in the subgroup with CD3+CD16+CD56 + ≤Me (low). When selecting a narrow subgroup (CD8+CD279+ high and CD3+CD16+CD56+ high), the frequency of pCR was 87,5 % vs 27,3 % in the group with both low indicators.Conclusion: The high content of CD8+CD279+ and CD3+CD16+CD56+ in the tumor sample before the treatment start was a predictor of high sensitivity to NACT and is associated with a higher frequency of pCR.Исследования последних лет показали, что тройной-негативный рак молочной железы (ТН РМЖ) характеризуется наибольшей мутационной нагрузкой и иммуногенностью по сравнению с другими молекулярно-генетическими подтипами, а также более высокой степенью инфильтрации опухоль-инфильтрирующими лимфоцитами (tumor-infiltrating lymphocytes — TILs), которые играют важнейшую роль в формирования противоопухолевого иммунитета и реализации ответа на лечение. Существенным недостатком стандартного иммуногистохимического метода определения TILs является невозможность полноценной оценки субпопуляционного состава иммунного инфильтрата, в том числе его минорных популяций.Целью данного исследования было изучение субпопуляционного состава лимфоидного инфильтрата при ТН РМЖ у пациентов, получавших неоадъювантную химиотерапию (НАХТ), и его влияние на достижение полного патоморфологического ответа на лечение (pCR = RCB 0).Материалы и методы: В исследование включено 90 пациенток с первично-операбельным (40 %) и неоперабельным местнораспространенным (60 %) ТН РМЖ, получавших НАХТ по схеме: АС 1 раз в 2 недели, далее 12 еженедельных введений паклитаксел 80 мг/м2 + карбоплатин AUC2. Субпопуляционный состав TILs оценивался в образцах core-биопсии до начала НАХТ у всех больных. Анализ осуществлялся методом проточной цитофлуориметрии. Проведена клинико-иммунологическая оценка по следующим девяти субпопуляциям лимфоцитов: CD3+CD4+, CD3+CD8+, CD4+CD25highCD127–/low, CD3–CD19+, CD3–CD16+CD56+, CD3+CD16+CD56+, CD4+CD25+, CD8+CD279+, CD4+CD279+.Результаты: Частота pCR составила 51,1 %. Общее содержание TILs в группах с полным и неполным патоморфозом (RCB 0 против RCB I–III) статистически не различалось (р = 0,271). При анализе субпопуляционного состава для популяций CD3+CD8+, CD3–CD16+CD56+, CD3+CD16+CD56+, CD3+CD4+, CD3–CD19+, CD4+CD25+, CD4+CD25highCD127–/low и CD4+CD279+ не было выявлено статистически значимых различий между медианными значениями в группах с полным и неполным патоморфозом. При исследовании популяции CD8+CD279+ выявлен более высокий уровень данных клеток у пациентов, достигших pCR / RCB 0 (медиана 18,6 % против 12,3 % при RCB I–III) (р = 0,033). При уровне CD8+CD279+ выше медианы (high) частота pCR составила 61,1 % против 35 % в подгруппе c содержанием CD8+CD279+ менее или равно медианы (low). Несмотря на отсутствие статистически значимых различий в содержании CD3+CD16+CD56+ (NKT-клеток) в группах с полным и неполным патоморфозом (р = 0,091), были выявлены численные различия в медианах: 9,9 % и 8,3 % соответственно. При уровне CD3+CD16+CD56+(NKT) выше медианы (high) частота pCR составила 63 % против 35,7 % в подгруппе c содержанием CD3+CD16+CD56+ менее или равно медианы (low). При выделении узкой подгруппы (CD8+CD279+ high и CD3+CD16+CD56+ high) частота полных патоморфологических регрессий в ней составила 87,5 % против 27,3 % при низких обоих показателях.Вывод: Таким образом, исходное высокое содержание CD8+CD279+ и CD3+CD16+CD56+ в опухоли явилось предиктором высокой чувствительности к НАХТ и ассоциировалось с большей частотой полных патоморфологических ответов

The specific features of T cell immunity in breast cancer

The fact that the formation and growth of malignancies occur with pronounced immune impairments is beyond question now. In the past de- cades, great progress has been made in the studies of the immunology and immunotherapy of malignancies, including breast cancer. Despite intensive studies of the specific features of cell immunity in breast cancer, many points remain to be inadequately studied sofar and the avail- able information is controversial and scarce, which calls for further studies

HETEROGENEITY OF NK AND NKT LYMPHOCYTE POPULATIONS IN HEALTHY DONORS

Natural killer(NK) and  NKT lymphocytes are important components of innate immunity, and compose a first-line defense against cancer. These populations are characterized by high heterogeneity and are divided into several subpopulations, by differences in functional activity as well as CD56  and CD16  expression. Studying  heterogeneity for these  lymphocyte populations in healthy  donors  is important, due  to imbalance between  different  lymphocyte subsets in cancer patients. Changes in the ratio of these subpopulations may be of prognostic and clinical  significance in malignant diseases. The present  study was conducted with peripheral blood  lymphocytes in 50 healthy  donors. When  analysing  population of NK  lymphocytes we have identified 18.0±11.3% of antigen-positive cells, their fluctuations ranged  from 7.6 to 29.2%, whereas average number of cells with  CD3-CD56+ and  CD3-CD16+   phenotypes was equal  to 16,2±8.1%, and  11,0±6.7%, respectively. The  subpopulation analysis  showed  that  the  primary  pool  of NK  cells  was presented by CD56dimCD16dim cells  by  52.3±19.9 percent.  We  detected  minor   subpopulations,  e.g.,  CD56dimCD16bright,  CD56-CD16+, CD56brightCD16- (0.3±0.2%, 1.7±0.9%, and  1.3±0.6%,  respectively). Search  for  intracellular perforin has revealed  that the number of CD56+Perf+ cells comprized 25.1±14.8%, CD16+Perf+, 23.8±16.0%. Cytometric analysis showed that perforin is found, predominantly, in CD56dimCD16dim NK lymphocytes, whereas the cells with CD56dimCD16bright, CD56-CD16+, CD56brightCD16- immunophenotypes did not produce perforin. For the first time, we have discovered a subpopulation of NK cells with the СD56dimCD16dim immunophenotype that did not contain intracellular perforin (2.0%).  The NKT cell population with СD3+CD16/СD56+  phenotype was detected in 7.1% (25% – 3.45; 75% – 8.75) antigen-positive cells, within a range of 2.5 to 11.9%. Analysis with a combination of monoclonal antibodies CD3/CD56/CD16 has shown that the number of CD3+ CD56+ cells was 4.33% (25% – 2.25; 75% – 7.3), whereas the number of CD3+CD16+ was 3.087% (25% – 0.9; 75% – 6.2). These  data  demonstrate that  the differences in results  between  the CD3/CD16/CD56, and  CD3/CD16 test systems are statistically significant  (p < 0.05). It was shown that the primary-pool NKT-cells are CD56+CD16- cells, whose number is about 5.45% (25% – 2.95; 75% – 7.3) among  total CD3+ lymphocyte population. Two minor subpopulations were also detected which differed in expression  of CD56 and CD16 antigens. Hence, the level of CD56-CD16+ cells was 3% (25% – 0.25; 75% – 3.05),  and the number of CD56+CD16+ was equal to 0.67% (25% – 0.25; 75% – 0.9). Hence, the observed wide phenotypic diversity of NK and NKT-cells reflects their  ability  to exert  various  functional activities.  This  study, showing  high  heterogeneity of NK  and  NKT lymphocytes, may serve as a basis for the study of imbalances between  different  subpopulations of these cells in cancer patients

DENDRITIC CELL-BASED VACCINE THERAPY IN PATIENTS WITH RENAL CELL CARCINOMA

Objective: to study the efficiency and tolerance of autologous vaccine therapy based on dendritic cells (DC) in patients with renal cell carcinoma (RCC) and to examine changes in immunological parameters and their association with the efficiency of the therapy. Subjects and methods. Twenty-nine patients with RCC received autologous vaccine therapy based on DC in 2002 to 2008. Therapy was performed in the induction mode in 16 patients before disease progression and in the adjuvant mode (8 vaccinations) in 13 patients after radical nephrectomy (grade III) or radical metastasectomy. Peripheral blood monocyte-derived DCs treated with autologous tumor lysate were used to prepare the vaccine. Results. In a group of 16 patients with distant metastases, partial regressions were recorded in 2 (12.5%) patients and long (> 6-month) stabilizations of a tumor process were observed in other 2 (12.5%) patients. The median time prior to progression was 3 (range 1.5-12) months. Thirteen patients on adjuvant treatment did not achieve the median time to progression: 4 patients showed no signs of disease progression ?12 to ?25 months after metastasectomy. Patients with a clinical effect (disease regression or long stabilization) showed a significant increase in the populations of CD3+CD8+ and CD3-CD16+ T lymphocytes (natural killers (NK) cells) after 3 vaccinations from 23.3 to 27.2% (p = 0.018) and from 15.17 to 20.3%, respectively (p = 0.03). Prior to vaccine therapy, the count of CD3+CD16+-NK cells was thrice greater in patients with the progressive disease than that in the donor group - 11.2 and 3.5%, respectively. The baseline count of CD4+CD25+ Т lymphocytes in patients with progressive disease was also significantly higher than that in patients with the clinical effect - 12.01 and 5.6%, respectively. Conclusion. In patients with RCC, DC-based vaccine therapy is able to induce a specific anti-tumor immune response that is transformed into the clinical effect in some cases. The baseline count of suppressor T lymphocyte (NKT and T-reg) populations may be a factor that predicts the efficiency of autologous DC-based vaccine therapy in patients with RCC. This immunotherapeutic approach merits further study, by defining the indications for its application in patients with RCC

Modern approaches to kidney cancer immunotherapy

Kidney cancer is a heterogeneous group of malignant tumors that develop from cells of the proximal convoluted tubules of the kidney. In Russia renal cell carcinoma holds the 2nd place after prostate cancer among tumors of genitourinary system. The main method of renal cell carcinoma treatment is radical nephrectomy, at the same time, high resistance of kidney cancer to chemotherapy and a weak response to hormone treatment are noted, and the effectiveness of cytokine therapy (interleukin 2, interferon alfa) does not exceed 18–20 %. The introduction into clinical practice of modern immune system affecting drugs has changed the disease prognosis for many patients with various malignant neoplasms. Currently, active development of immunotherapeutic drugs directed against inhibitory receptors of T-cells, the so-called “immunity control points” takes place, the most studied among these drugs are anti-CTLA-4 (cytotoxic T-lymphocyte associated protein 4) and anti-PD-1 (рrogrammed cell death pathway 1)/PD-L1 (programmed death ligand 1) monoclonal antibodies. In this review a detailed description of the PD-1 receptor and its PD-L1 ligand, as well as the prognostic and predictive significance of their expression in various types of renal cell carcinoma and the role in suppressing the antitumor T-cell immune response are presented. Blockade of PD-1/PD-L1 enhances antitumor immunity reducing the amount and/or immunosuppressive activity of regulatory T-cells (suppressors) and restoring the activity of effector T-cells that leads to an enhancement of the antitumor immune response. The blockade of PD-1 also stimulates proliferation of memory B-cells. In this regard, drugs that suppress the function of PD-1 are now widely used in the treatment of cancer including kidney cancer. The authors provide a list of promising drugs acting on PD-1/PD-L1 system used in renal cell carcinoma: nivolumab, pembrolizumab and some others. The results of clinical studies se of immunotherapeutic drugs in kidney cancer are analyzed