Адрес для переписки:Боголюбова Аполлинария Васильевна ФГБУН «Институт молекулярной биологии им. В.А. Энгельгардта» РАН 119991, Россия, Москва, ул. Вавилова, 32. Тел.: 8 (499) 135-99-64. Факс: 8 (499) 135-14-05. E-mail: apollinariya.bogolyubova@gmail.com Sciences 119991, Russian Federation, Moscow, Vavilov str., 32. Phone: 7 (499) 135-99-64. Fax: 7 (499) 135-14-05. E-mail: apollinariya.bogolyubova@gmail.com Образец цитирования: А.В. Боголюбова, Г.А. Ефимов, М.С. Друцкая, С.А. Недоспасов, «Иммунотерапия опухолей, основанная на блокировке иммунологических контрольных «точек» («чекпойнтов»)» // Медицинская иммунология, 2015. Т. 17, № 5. С. 395-406. doi: 10.15789/1563-0625-2015-5-395-406 © Боголюбова А.В. и соавт., 2015 For citation: A.V. Bogolyubova, G.A. Efimov, M.S. Drutskaya, S.A. Nedospasov, "Cancer immunotherapy based on the blockade of immune checkpoints", Medical Immunology (Russia) /Meditsinskaya Immunologiya, 2015, Vol. 17, no. 5, pp. 395-406. doi: 10.15789/1563-0625-2015 Резюме. Иммунологические контрольные «точки» (ИКТ, англ. Immunological checkpoints) -это система ингибиторных механизмов, которые регулируют активацию иммунного ответа, препятствуя запуску аутоиммунных процессов, а также модулируют его, уменьшая вызванные иммунными клет-ками повреждения в органах и тканях. Опухолевые клетки могут использовать такие контрольные точки для предотвращения активации опухоль-специфических лимфоцитов, таким образом, приоб-ретая устойчивость к действию иммунной системы. Одним из перспективных методов иммунотера-пии опухолей является блокировка ингибирующего сигнала, передающегося через иммунологические контрольные точки, приводящая к реактивации противоопухолевого иммунного ответа. Поскольку большая часть контрольных точек функционирует за счет взаимодействий лиганд-рецептор, одна из стратегий современной противоопухолевой терапии основана на создании терапевтических моно-клональных антител, блокирующих лиганд или рецептор, а также растворимых рекомбинантных ре-цепторов, которые могли бы конкурировать за лиганд и таким образом модулировать передачу сигна-ла. В последние годы в этом направлении иммунотерапии опухолей получены впечатляющие успехи, однако потенциальной платой за вмешательство в естественные супрессорные механизмы является развитие аутоиммунных реакций. .V. et al. Боголюбова А.В. и др. Medical Immunology (Russia) Address for correspondence: Bogolyubova Apollinariya V. Engelhardt Institute of Molecular Biology of Russian Academy of /Meditsinskaya ImmunologiyaМедицинская Иммунология the immune cell-mediated damage of tissues and organs. Tumor cells may utilize these checkpoints to prevent the activation of tumor-specific lymphocytes, thereby acquiring resistance against the immune response. The blockade of inhibitory signal that is transduced in immune checkpoints leading to the reactivation of antitumor immune response is a promising method of tumor immunotherapy. Since the majority of immune checkpoints are based on the ligand-receptor interactions, one of contempor...
Non-alcoholic fatty liver disease (NAFLD) is a group of conditions closely associated with obesity that are among the most common and socially significant liver diseases in the modern Western world. The emergence and progression of NAFLD from simple steatosis to non-alcoholic steatohepatitis with the subsequent development of fibrosis are the leading factors in the pathogenesis of a significant proportion of the most severe liver pathologies, such as cirrhosis and hepatocellular carcinoma, as well as extrahepatic metabolic complications of NAFLD, such as insulin resistance and type 2 diabetes mellitus. The inflammatory component is one of the most important factors in the pathogenesis of NAFLD, particularly in the context of the progression of simple steatosis to non-alcoholic steatohepatitis. At the same time, the role of the most important mediators of the inflammatory response, innate immunity receptors and the Toll-like receptors in particular, in the pathogenesis of NAFLD has been poorly studied. In the present work, we first used the bioinformatics analysis of the publicly available gene expression databases to demonstrate that only TLR1, TLR2, TLR3 and TLR4 were significantly expressed in the healthy human liver. We then used the reverse transcription PCR to measure the mRNA expression levels of TLR2, TLR3, and TLR4, as well as those of the important pro-inflammatory mediators tumor necrosis factor (TNF) and interleukin-6 (IL-6), in the liver biopsy specimens obtained from 20 patients with NAFLD (simple steatosis, n = 10; non-alcoholic steatohepatitis, n = 10), as well as from 4 obese patients with clinical suspicion for NAFLD but no histological signs of NAFLD in their liver biopsies. We found a significant increase in the expression of TLR2, TLR3 and TLR4 mRNA in liver biopsy samples obtained from patients with non-alcoholic steatohepatitis as compared to those obtained from controls without histological signs of NAFLD. We were also able to demonstrate the association between the hepatic levels of TLR2, TLR3 and TLR4 mRNAs with the histological degree of liver damage as evidenced by the degree of steatosis and balloon dystrophy of hepatocytes, as well as with the plasma levels of uric acid, the important endogenous stimulator of innate immunity. Our data indicate the possible involvement of innate immunity, particularly the Toll-like receptors, in the pathogenesis of NAFLD.
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