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

Место иммуноонкологии в лечении немелкоклеточного рака легкого

Non–small cell lung cancer (NSCLC) is the leading cause of cancer related mortality worldwide. Many patients present with metastatic disease and traditional CT treatment fails to provide long- term benefit for most patients. Patients with driver mutations demonstrate substantially better response rate and progressionfree survival when the appropriate targeted agents are used, but only approximately 25%-30% of patients with NSCLC have actionable mutations. Novel treatment options are clearly needed for patients with lung cancer. Immuno-oncology recently has been identified as effective second line therapy of NCSLC. Almost all of this progress has been due to the development of PD‑1 and PD-L1 inhibitors. In this review, we explore the data currently available for these agents.Немелкоклеточный рак легкого (НМРЛ) является ведущей причиной смертности от онкологических заболеваний во всем мире. При применении стандартной химиотерапии не удалось достигнуть хороших результатов долгосрочной выживаемости у пациентов с метастатическим НМРЛ. При наличии драйверных мутаций назначение таргетной терапии позволяет добиться хорошего ответа и значительного увеличения показателя выживаемости без прогрессирования. Однако только около у 25%-30% пациентов с НМРЛ выявляются эти мутации. Таким образом, для лечения рака легкого актуальна разработка новых подходов терапии. Недавно было показано, что иммуноонкология является эффективным подходом во второй линии терапии НМРЛ. Этот прогресс был достигнут благодаря разработке препаратов ингибиторов рецептора PD‑1 и лиганда PD-L1. В этом обзоре мы рассмотрим данные исследований, доступные для этих препаратов в настоящее время

ИММУНООПОСРЕДОВАННЫЕ НЕЖЕЛАТЕЛЬНЫЕ ЯВЛЕНИЯ, СВЯЗАННЫЕ С ЛЕЧЕНИЕМ ПРЕПАРАТАМИ, БЛОКИРУЮЩИМИ КОНТРОЛЬНЫЕ ТОЧКИ Т-ЛИМФОЦИТОВ

In recent years, immunotherapy is the main emphasis approach for malignant tumors treatment due to the development and registration of a new class of drugs –immune checkpoint inhibitors. Results of the randomized clinical trials, which showed a benefit in overall survival in comparison with standard therapy, was the basis for registration of this class of medicines [1–3]. Their toxicity profile is more favorable. However, the adverse reactions, which accrues during immunotherapy, are essentially new and different from standard chemotherapy. The standard management algorithm compensates the variety of immunemediated adverse reactions [4]. Early detection and timely treatment is necessary for the successful management of these adverse reactions. В последние годы основной акцент в лекарственном лечении злокачественных опухолей делается на иммунотерапию.Это обусловлено разработкой и регистрацией нового класса препаратов – блокаторов контрольных точек иммунного пути. Основанием для регистрации этого класса препаратов послужили результаты рандомизированных клинических исследований, показавших преимущество этих препаратов по сравнению со стандартной терапией в общей выживаемости [1–3]. Более благоприятным оказался их токсический профиль. Однако те осложнения, с которыми пришлось столкнуться клиницистам, имели принципиально новый, отличный от обусловленных стандартными цитостатиками характер. Многообразие побочных иммуноопосредованных реакций компенсируется стандартным алгоритмом их коррекции [4]. Раннее выявление и своевременное лечение необходимо для успешного купирования этих осложнений