Les Liaisons dangereuses: парадоксальные результаты цитотоксической активности опухолевых макрофагов

Роль иммунной системы в прогрессии опухолей изучается уже больше века, начиная с гипотезы Пауля Эрлиха о ее значении в сдерживании формирования онкологических заболеваний. Развитие онкоиммунологии позволило подтвердить эту гипотезу и выявить механизмы сложных взаимодействий клеток иммунной системы как с чужеродными агентами, так и с трансформированными клетками организма. ключевую роль в уничтожении опухолевых клеток играют макрофаги, естественные киллеры и Т-лимфоциты. Среди них особое внимание уделяется макрофагам, ассоциированным с опухолью. Опухолевые клетки способны модулировать активность макрофагов, трансформируя их в клетки с иммуносупрессорными свойствами, способствующими ангиогенезу и ремоделированию внеклеточного матрикса. Таким образом, наибольшую популяцию макрофагов, ассоциированных с опухолью, составляют клетки, обладающие противовоспалительным/проопухолевым фенотипом (М2).
Макрофаги провоспалительного фенотипа (М1) характеризуются продукцией провоспалительных цитокинов, активных форм кислорода и выраженной цитотоксической активностью. Они способны уничтожать опухолевые клетки как напрямую, так и опосредованно, вовлекая другие иммунные клетки. Традиционно цитотоксическая активность макрофагов считается важным механизмом ограничения роста опухолей, однако в ряде случаев ее недостаточно для эффективного контроля над опухолевым процессом. На сегодняшний день есть данные о том, что клетки опухоли способны вырабатывать механизмы защиты от макрофагальной цитотоксичности и приобретать способность ее преодолевать. Более того, опухолевые клетки, появляющиеся в результате взаимодействия с цитотоксическими макрофагами, обладают и другими свойствами, обеспечивающими их ростовые преимущества.
Данный обзор посвящен описанию новой проопухолевой функции макрофагов М1, традиционно считающихся противоопухолевыми.

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