ИММУНОЛОГИЧЕСКИЕ АСПЕКТЫ ОПУХОЛЕВО-ИНФИЛЬТРАТИРУЮЩИХ ЛИМФОЦИТОВ ПРИ РАКЕ МОЛОЧНОЙ ЖЕЛЕЗЫ
Ключевые слова:
рак молочной железы, инфильтрирующие опухоль лимфоциты, CD8 T-клетки, FOXP3Аннотация
Опухолевые инфильтрирующие лимфоциты (TIL) играют важную роль в опосредовании ответа на химиотерапию и улучшении клинических исходов при всех подтипах рака молочной железы. Тройной негативный рак молочной железы (TN), скорее всего, имеет опухоли с > 50% лимфоцитарной инфильтрацией, называемой раком молочной железы с преобладанием лимфоцитов, и получает наибольшее преимущество в выживаемости при каждом увеличении TIL на 10%. Большинство случаев рака молочной железы HER2+ имеют такой же уровень иммунного инфильтрата, что и рак молочной железы TN, но наличие TIL не показало такого же преимущества в выживаемости. Для рака молочной железы HER2+ Т-клетки 1 типа, либо повышенная инфильтрация опухоли TBET+, либо повышенное количество HER2-специфических CD4+ Т-клеток 1 типа в периферической крови связаны с лучшими результатами. Гормональные рецептор-положительные HER2-отрицательные опухоли, как правило, имеют наименьший иммунный инфильтрат, но являются единственным подтипом рака молочной железы, для которого характерен худший прогноз с повышенным инфильтратом регуляторных Т-клеток FOXP3. Примечательно, что все подтипы рака молочной железы имеют опухоли с низким, средним или высоким инфильтратом TIL. Опухоли с высоким TIL также могут иметь повышенную экспрессию PD-L1, что может быть причиной того, что рак молочной железы TN, по-видимому, демонстрирует наиболее сильный клинический ответ на терапию ингибиторами иммунных контрольных точек, но необходимы дальнейшие исследования. С другой стороны, опухоли со средним или низким уровнем иммунного инфильтрата до лечения могут получить пользу от вмешательства, которое может увеличить TIL, особенно Т-клетки типа 1. Примеры таких вмешательств включают определенные виды цитотоксической химиотерапии, лучевой терапии или вакцинотерапии. Таким образом, систематическая оценка TIL и конкретных популяций TIL может помочь как в определении прогноза, так и в соответствующей последовательности лечения рака молочной железы.
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