mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-ARO-3191mimmun-3191Research ArticleОБЗОРЫREVIEWSПобочные реакции ингибиторов иммунных контрольных точекAdverse reactions of immune checkpoint inhibitorshttps://orcid.org/0009-0005-9693-5461ЗагидуллинаЭ. Р.ZagidullinaE. R.

Загидуллина Эмилия Рафилевна – студент 

295051, Республика Крым, г. Симферополь, бул. Ленина, 5/7 

Тел.: 8 (978) 223-90-66 

Student, S. Georgievsky Medical Institute 

Simferopol 

m.igarasi@yandex.ruhttps://orcid.org/0000-0003-1693-3190КалиберденкоВ. Б.KaliberdenkoV. B.

К.м.н. Доцент кафедры внутренней медицины № 2

г. Симферополь 

PhD (Medicine), Associate Professor, Department of Internal Medicine No. 2 

Simferopol 

vit_boris@mail.ruhttps://orcid.org/0009-0008-1130-7709КулиеваЭ. Р.KulievaE. R.

Ассистент кафедры внутренней медицины № 2 

г. Симферополь 

Assistant Professor, Department of Internal Medicine No. 2 

Simferopol 

elvinaemir20@gmail.comhttps://orcid.org/0009-0009-9054-7926БетерВ. С.BeterV. S.

Студент 

г. Симферополь 

Student, S. Georgievsky Medical Institute 

Simferopol 

vfridman926@gmail.comhttps://orcid.org/0009-0006-4936-5088ПронькинаТ. С.PronkinaT. S.

Студент 

г. Симферополь 

Student 

Simferopol 

ytochkakryakrya@gmail.comhttps://orcid.org/0009-0000-9635-8960КушнерВ. А.KushnerV. A.

Студент

г. Симферополь 

Student 

Simferopol 

kushnervaleria22@mail.ruhttps://orcid.org/0009-0008-4533-326XТаранВ. В.TaranV. V.

Студент

г. Симферополь 

Student 

Simferopol 

vi.ku.sha2020@yandex.ruОрдена Трудового Красного Знамени Медицинский институт имени С.И. Георгиевского ФГАОУ ВО «Крымский федеральный университет имени В.И. Вернадского»РоссияS. Georgievsky Medical Institute, V. Vernadsky Crimean Federal UniversityRussian Federation202506062025273485500Copyright © Загидуллина Э.Р., Калиберденко В.Б., Кулиева Э.Р., Бетер В.С., Пронькина Т.С., Кушнер В.А., Таран В.В., 20252025Загидуллина Э.Р., Калиберденко В.Б., Кулиева Э.Р., Бетер В.С., Пронькина Т.С., Кушнер В.А., Таран В.В.Zagidullina E.R., Kaliberdenko V.B., Kulieva E.R., Beter V.S., Pronkina T.S., Kushner V.A., Taran V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/3191

Цель работы – анализ нежелательных реакций, связанных с применением ингибиторов иммунных контрольных точек в качестве противоопухолевой терапии. Литературный обзор включает в себя анализ научных работ из баз данных PubMed, Embase, eLIBRARY, «КиберЛенинка» и Web of Science, CNKI и MEDLINE. Ключевые слова: «ингибиторы иммунных контрольных точек», «иммуноопосредованные нежелательные явления», «иммунные контрольные точки», «противоопухолевая терапия», «иммунная система», «побочные явления». Открытие иммунных контрольных точек (ИКТ) и последующая разработка соответствующих ингибиторов за последнее десятилетие стали революционными прорывами в области лечения рака. ИКТ открыли новую эпоху противоопухолевой терапии и действительно улучшили прогноз онкологических больных. Противоопухолевое действие ингибиторов ИКТ основано на блокаде сигнальных путей CTLA-4 и PD-1/PD-L1 и усилении противоопухолевой активности лимфоцитов. Однако ингибирование ИКТ может провоцировать нарушение регуляции иммунных ответов и появление нового вида нежелательных реакций, связанных с изменением активности иммунокомпетентных клеток в организме – побочные явления, связанные с иммунитетом (IrAEs). Наиболее частыми являются кожные, гепатобиллиарные и эндокринные побочные явления. Стоит отметить, что частота возникновения нежелательных явлений в сердечно-сосудистой и нервной системах невелика от общего числа случаев, но последствия приводят к инвалидизации пациентов и часто летальны. В настоящее время для лечения нежелательных явлений в основном используются гормональные препараты, иммунодепрессанты и антагонисты цитокинов. Однако эти методы лечения могут вызывать подавление иммунной системы у пациентов, тем самым ослабляя их противоопухолевый иммунный ответ. На данный момент остается много нерешенных проблем, связанных с иммуноопосредованными нежелательными явлениями, таких как неясные механизмы и биомаркеры, способы более раннего выявления иммуноопосредованных нежелательных явлений и разработка более совершенных индивидуальных методов лечения иммуноопосредованных нежелательных явлений. Исследователи полагают, что при более широком применении иммунотерапии и более глубоком изучении ингибиторов ИКТ и связанных с ними побочных иммунных реакций вышеуказанные проблемы могут быть решены, что сможет в полной мере реализовать потенциал ИКТ

Our objective was to consider the adverse reactions associated with usage of immune checkpoint inhibitors (ICI). The literature review includes a search for scientific papers from the databases PubMed, Embase, eLibrary, CyberLeninka and Web of Science, CNKI and MEDLINE by the following keywords: “immune checkpoint inhibitors”, “immune-mediated adverse events”, “immune checkpoints”, “antitumor therapy”, “immune system”, “side effects”. Over the past decade, the discovery of immune checkpoints followed by development of appropriate inhibitors have provided breakthrough advances in cancer treatment. The ICI-based therapy has opened a new era of antitumor treatment and has really improved clinical prognosis in the cancer patients. The antitumor effect of ICI is based on the blockade of CTLA-4 and PD-1/PD-L1 signaling pathways, thus promoting antitumor activity of lymphocytes. However, inhibition of immune checkpoints may also provoke dysregulation of immune responses and appearance of a new type of adverse reactions associated with changed activity of immunocompetent cells in the host organism, i.e., immunerelated side effects (irAEs). The most common side effects concern skin, hepatobiliary, and endocrine systems. Of note, the frequency of adverse events affecting cardiovascular and nervous systems is relatively low among total number of cases, but the consequences lead to disability of patients and are often fatal. Currently, hormonal drugs, immunosuppressants, and cytokine antagonists are mainly used to treat adverse events of ICI. However, these treatments may cause suppression of the immune system in patients, thereby weakening their antitumor immune response. There are still many unresolved issues related to irAEs, such as unclear mechanisms and biomarkers, tools for early detection of these adverse events, and development of more advanced individual treatments for such complications. The researchers believe that the above problems can be solved with wider use of immunotherapy, deeper studies on ICI and related adverse immune reactions, thus enabling full-scale implementation of ICI potential in anticancer therapy and improving clinical outcomes. Accordingly, the topic is quite relevant and requires close attention from practitioners and scientists.

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