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Злокачественные опухоли

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УЛЬТРАЗВУКОВАЯ АБЛАЦИЯ ОПУХОЛИ: ИММУННЫЕ ЭФФЕКТЫ И ПЕРСПЕКТИВЫ ИНТЕГРАЦИИ В СОВРЕМЕННЫЕ ПРОГРАММЫ ЛЕЧЕНИЯ ГЕНЕРАЛИЗОВАННОГО РАКА

https://doi.org/10.18027/2224-5057-2018-8-2-31-42

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Аннотация

Несмотря на революционные открытия последних лет в области молекулярной онкологии и иммунологии, выживаемость при генерализованных формах злокачественных новообразований не превышает 20–30 %, поэтому поиск новых терапевтических подходов остается актуальной задачей. Дальнейший прогресс, в частности, связывают с повышением иммуногенности опухолей, индукцией воспалительного фенотипа и блокадой механизмов иммуносупрессии. Решению этих задач может способствовать ультразвуковая аблация (УЗА), которая занимает особое место среди аналогичных методик, поскольку вызывает быстрый иммунный ответ, обладает неинвазивностью и низкой локальной токсичностью, позволяет манипулировать параметрами физического воздействия, допускает многократное применение, относительно недорога и не требует длительной госпитализации. Помимо циторедукции и снижения системных иммунносупрессивных сигналов, УЗА создает в организме депо лизированных клеток и считается способом вакцинирования in situ. Постаблативная иммуногенная клеточная смерть стимулирует начальные фазы иммунного цикла и способствует генерации популяций CD4+ и CD8+ цитотоксических Т-лимфоцитов. Однако инфильтрация зоны соникации и отдаленных метастазов активированными эффекторными клетками в короткие сроки приводит к запуску защитных механизмов со стороны опухоли, в частности экспрессии PD-1L, что не позволяет достичь стойких абскопальных эффектов и контроля заболевания. Поэтому сегодня УЗА чаще рассматривается как один из элементов комбинированных стратегий, влияющих на различные фазы иммунного цикла (агонисты TLR, GM-CSF, цитокины, блокаторы CTLA-4, PD-1 / PD-1L, агонисты стимуляторных контрольных точек, адоптивная терапия и др.) Доклинические исследования показали повышение процента абскопальных эффектов и улучшение выживаемости при сочетании УЗА с иммунотерапией, а также предпосылки для снижения доз ингибиторов контрольных точек и частоты нежелательных явлений. В случае прогрессирования на фоне иммунотерапии УЗА может быть способом повторной антигенной стимуляции и расширения клонального репертуара эффекторных клеток. Экспериментальные данные легли в основу дизайна ряда текущих клинических исследований в РФ и за рубежом, которые в ближайшей перспективе должны уточнить ряд методологических аспектов, а также показать роль и место УЗА в комбинированном лечении пациентов с диссеминированным раком.

Об авторе

Г. Н. Мачак
ФГБУ «Национальный медицинский исследовательский центр травматологии и ортопедии имени Н.Н. Приорова» Министерства здравоохранения РФ
Россия

Геннадий Н. Мачак - доктор медицинских наук.

Москва



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Для цитирования:


Мачак Г.Н. УЛЬТРАЗВУКОВАЯ АБЛАЦИЯ ОПУХОЛИ: ИММУННЫЕ ЭФФЕКТЫ И ПЕРСПЕКТИВЫ ИНТЕГРАЦИИ В СОВРЕМЕННЫЕ ПРОГРАММЫ ЛЕЧЕНИЯ ГЕНЕРАЛИЗОВАННОГО РАКА. Злокачественные опухоли. 2018;8(2):31-42. https://doi.org/10.18027/2224-5057-2018-8-2-31-42

For citation:


Machak G.N. ULTRASOUND TUMOR ABLATION: IMMUNE EFFECTS AND PERSPECTIVES OF INTEGRATION IN THE MODERN TREATMENT OF ADVANCED CANCER. Malignant tumours. 2018;8(2):31-42. (In Russ.) https://doi.org/10.18027/2224-5057-2018-8-2-31-42

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