oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2023-22-4-109-117oncotomsk-2686Research ArticleОБЗОРЫREVIEWSРезистентность к ингибиторам контрольных точек иммунитета в лечении метастатического рака почкиResistance to immune checkpoint inhibitors in the treatment of metastatic renal cancerhttps://orcid.org/0000-0002-8461-9243ИзмайловА. А.IzmailovA. A.

Измайлов Адель Альбертович, доктор медицинских наук, главный врач 

450054, г. Уфа, пр. Октября, 73/1

Adel A. Izmailov, MD, DSc, Chief Physician, 

73/1, Oktyabrya Ave., 450054, Ufa

izmailov75@mail.ruhttps://orcid.org/0000-0002-2488-597XРахимовР. Р.RakhimovR. R.

Рахимов Радмир Радимович, кандидат медицинских наук, врач-онколог отдела противоопухолевой лекарственной терапии 

450054, г. Уфа, пр. Октября, 73/1

Radmir R. Rakhimov, MD, PhD, Oncologist of the Department of Antitumor Drug Therapy, 

73/1, Oktyabrya Ave., 450054, Ufa

radmir-rr@mail.ruhttps://orcid.org/0000-0003-0996-5995СултанбаевА. В.SultanbayevA. V.

Султанбаев Александр Валерьевич, кандидат медицинских наук, заведующий отделом противоопухолевой лекарственной терапии 

450054, г. Уфа, пр. Октября, 73/1

Alexander V. Sultanbaev, MD, PhD, Head of the Department of Antitumor Drug Therapy, 

73/1, Oktyabrya Ave., 450054, Ufa

МеньшиковК. В.MenshikovK. V.

Меньшиков Константин Викторович, кандидат медицинских наук, врач-онколог отдела противоопухолевой лекарственной терапии; доцент кафедры онкологии с курсами онкологии и патологической анатомии 

450054, г. Уфа, пр. Октября, 73/1;450077, г. Уфа, ул. Заки Валиди, 47

Konstantin V. Menshikov, MD, PhD, Oncologist of the Department of Antitumor Drug Therapy; Associate Professor of the Department of Oncology with courses in Oncology and Pathological Anatomy, 

73/1, Oktyabrya Ave., 450054, Ufa;47, Zaki Validi St., 450077, Ufa

https://orcid.org/0000-0001-9499-5632ГилязоваИ. Р.GilyazovaI. R.

Гилязова Ирина Ришатовна, кандидат биологических наук, доцент кафедры медицинской генетики и фундаментальной медицины; старший научный сотрудник лаборатории молекулярной генетики человека 

450077, г. Уфа, ул. Заки Валиди, 47;450054, г. Уфа, пр. Октября, 71

Irina R. Gilyazova, PhD, Associate Professor of the Department of Medical Genetics and Fundamental Medicine; Senior Researcher of the Laboratory of Human Molecular Genetics 

47, Zaki Validi St., 450077, Ufa;71, Octobrya Ave., 450054, Ufa

https://orcid.org/0009-0000-8375-3953ЗабелинВ. М.ZabelinV. M.

Забелин Вадим Максимович, студент 

117997, г. Москва, ул. Островитянова, 1

Vadim M. Zabelin, student, 

1, Ostrovityanova St., 117997, Moscow

https://orcid.org/0000-0001-5836-0066ИзмайловА. А.IzmailovA. A.

Измайлов Альберт Аделевич, аспирант 

125284, г. Москва, 2-й Боткинский пр-д, 3

Albert A. Izmailov, MD, Postgraduate, 

3, 2nd Botkinsky proezd, 125284, Moscow

ГАУЗ «Республиканский клинический онкологический диспансер» Минздрава Республики БашкортостанРоссияRepublican Clinical Oncology Center of the Ministry of Health of the Republic of BashkortostanRussian FederationГАУЗ «Республиканский клинический онкологический диспансер» Минздрава Республики Башкортостан; ФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава РоссииРоссияRepublican Clinical Oncology Center of the Ministry of Health of the Republic of Bashkortostan; Bashkir State Medical University of the Ministry of Health of the RussiaRussian FederationФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава России; ФГБНУ Институт биохимии и генетики Уфимского федерального исследовательского центра Российской академии наукРоссияBashkir State Medical University of the Ministry of Health of the Russia; Institute of Biochemistry and Genetics, Ufa Federal Research Centre of the Russian Academy of SciencesRussian FederationФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава РоссииРоссияN.I. Pirogov Russian National Research Medical University of the Ministry of Health of RussiaRussian FederationМосковский научно-исследовательский онкологический институт им. П.А. Герцена – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава РоссииРоссияP.A. Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre of the Ministry of Health of the RussiaRussian Federation202308092023224109117Copyright © Измайлов А.А., Рахимов Р.Р., Султанбаев А.В., Меньшиков К.В., Гилязова И.Р., Забелин В.М., Измайлов А.А., 20232023Измайлов А.А., Рахимов Р.Р., Султанбаев А.В., Меньшиков К.В., Гилязова И.Р., Забелин В.М., Измайлов А.А.Izmailov A.A., Rakhimov R.R., Sultanbayev A.V., Menshikov K.V., Gilyazova I.R., Zabelin V.M., Izmailov A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/2686

В последние 5 лет ингибиторы контрольных точек (ИКК), включая блокаторы анти-CTLA-4 и анти-PD-1/ PD-L1, изменили подходы к лекарственной терапии метастатического рака почки. Тем не менее у большого числа больных с распространенным раком почки развивается резистентность к иммунотерапии. В данной статье отражены причины, которые приводят к первичной и приобретенной резистентности к ИКК иммунитета при лечении метастатического рака почки. Цель исследования – изучить механизмы появления резистентности к ингибиторам контрольных точек при лечении метастатического рака почки. Материал и методы. Произведен поиск публикаций в системе Pubmed с 2010 по 2023 г. Найдено 286 статей, 59 из них использованы для написания обзора. Результаты. Существует много факторов, способствующих первичной или приобретенной резистентности к иммуноонкологическим препаратам, включая факторы, свойственные пациенту, факторы, связанные с опухолевой клеткой, факторы, присущие опухолевому микроокружению. Заключение. В рамках клинических исследований изучаются инновационные подходы к преодолению резистентности к моноклональным антителам. С появлением новых данных становятся более понятными клеточный состав и роль микроокружения опухоли в появлении резистентности к иммунотерапии. Появляются новые биомаркеры, которые помогут выявить наилучших кандидатов для иммунотерапии метастатического рака почки. Однако они требуют дальнейшего изучения.

Over the past 5 years, checkpoint inhibitors including anti-CTLA-4 and anti-PD-1/PD-L1 blockers have changed approaches to therapy of metastatic renal cell cancer. However, more than 55 % of patients with advanced kidney cancer remain resistant to immunotherapy. This paper refects the causes that lead to primary and acquired resistance to immune checkpoint inhibitors during the treatment of metastatic renal cell cancer. The purpose of the study was to elucidate the mechanisms underlying resistance to checkpoint inhibitors during the treatment of metastatic kidney cancer. Material and Methods. A literature search was conducted using Pubmed database in the time interval between 2010 and 2023. We identifed 286 publications of which 59 were relevant for our review. Results. There are many factors that contribute to primary or acquired resistance to immunotherapy, including factors associated with the tumor cell as well as tumor microenvironment factors. Conclusion. Many innovative approaches to overcoming resistance to monoclonal antibodies are being investigated in clinical trials. In connection with the advent of new methods, the cellular composition of the tumor microenvironment and its role in the emergence of tumor resistance to immunotherapy are becoming increasingly clear. New biomarkers are emerging to help identify the best candidates for immunotherapy in metastatic kidney cancer. However, they require further study. 

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The authors declare that there are no conflicts of interest present.