Классическая лимфома Ходжкина: структура опухоли и прогностическое значение иммунного микроокружения

ОБЗОРЫ , , ,

А.А. Гусак, К.В. Лепик, Л.В. Федорова, В.В. Маркелов, В.В. Байков

НИИ детской онкологии, гематологии и трансплантологии им. Р.М. Горбачевой, ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова» Минздрава России, ул. Льва Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022

Для переписки: Артем Александрович Гусак, ул. Льва Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022; e-mail: artemgusak@yandex.ru

Для цитирования: Гусак А.А., Лепик К.В., Федорова Л.В., Маркелов В.В., Байков В.В. Классическая лимфома Ходжкина: структура опухоли и прогностическое значение иммунного микроокружения. Клиническая онкогематология. 2023;16(3):242–62.

DOI: 10.21320/2500-2139-2023-16-3-242-262

РЕФЕРАТ

Классическая лимфома Ходжкина (ЛХ) представляет собой уникальное злокачественное новообразование лимфатической системы, характеризующееся наличием опухолевых клеток (Ходжкина и Рид—Штернберга) в воспалительном и иммуносупрессивном микроокружении. Микроокружение ЛХ — комплексная динамичная среда, включающая иммунные клетки, стромальные элементы и компоненты внеклеточного матрикса, которые взаимодействуют друг с другом и с опухолевыми клетками. От характера этих взаимодействий во многом зависит как прогрессирование заболевания, так и ответ на терапию. В настоящее время возрастает интерес к изучению структуры и функции микроокружения ЛХ, его прогностического значения, потенциала его компонентов в качестве новых мишеней для лекарственной терапии. В последнее десятилетие значительно улучшились результаты лечения рефрактерных форм ЛХ, в частности, за счет применения ингибиторов PD-1 ниволумаба и пембролизумаба. Высокая чувствительность ЛХ к анти-PD-1-терапии обусловлена формированием PD-1/PD-L1-ассоциированной ниши в ткани опухоли. Основой ниши является интенсивная экспрессия PD-L1 опухолевыми клетками, макрофагами и экспрессия его рецептора PD-1 Т-клетками и М2-макрофагами. Накапливается все больше сведений о возможных механизмах противоопухолевого ответа у пациентов с ЛХ при анти-PD-1-терапии, противоречащих концепции классического CD8-опосредованного ответа при солидных опухолях. Вероятно, цитотоксические эффекты анти-PD-1-терапии в ткани ЛХ достигаются путем взаимодействия между опухолевыми клетками, макрофагами и CD4-позитивными Т-лимфоцитами. В обзоре представлены сведения о структурных и регуляторных взаимоотношениях опухолевых клеток и элементов микроокружения, описываются новые терапевтические подходы, основанные на использовании в качестве мишеней различных компонентов опухолевого микроокружения, суммированы имеющиеся к настоящему времени данные о возможности прогнозирования на основе изучения характеристик микроокружения ЛХ.

Ключевые слова: классическая лимфома Ходжкина, микроокружение, иммунные контрольные точки, поляризация макрофагов, иммуносупрессивная ниша.

Получено: 12 апреля 2023 г.

Принято в печать: 25 июня 2023 г.

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Статистика Plumx русский

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