Побочные реакции ингибиторов иммунных контрольных точек

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

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