Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press75510.17650/2313-805X-2025-12-1-31-40REVIEW ARTICLESОБЗОРНЫЕ СТАТЬИLes Liaisons dangereuses: the paradoxical outcomes of the cytotoxic activity of tumor macrophagesLes Liaisons dangereuses: парадоксальные результаты цитотоксической активности опухолевых макрофаговhttps://orcid.org/0000-0001-6132-9924KovalevaO. V.КовалеваО. В.
Russian Federation

Olga Vladimirovna Kovaleva  

24 Kashirskoe Shosse, Moscow 115522, Russia 

Ольга Владимировна Ковалева

Россия, 115522 Москва, Каширское шоссе, 24 

ovkovaleva@gmail.comhttps://orcid.org/0000-0002-3267-4232RashidovaM. A.РашидоваМ. А.
Russian Federation

 24 Kashirskoe Shosse, Moscow 115522, Russia 

Россия, 115522 Москва, Каширское шоссе, 24

https://orcid.org/0000-0001-5105-5763SinyovV. V.СиневВ. В.
Russian Federation

 24 Kashirskoe Shosse, Moscow 115522, Russia 

Россия, 115522 Москва, Каширское шоссе, 24

https://orcid.org/0009-0006-7262-990XMalashenkoO. S.МалашенкоО. С.
Russian Federation

 24 Kashirskoe Shosse, Moscow 115522, Russia 

Россия, 115522 Москва, Каширское шоссе, 24

https://orcid.org/0000-0003-2137-1866GratchevA. N.ГрачевА. Н.
Russian Federation

 24 Kashirskoe Shosse, Moscow 115522, Russia 

Россия, 115522 Москва, Каширское шоссе, 24

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России1501202512131401404202514042025Copyright ©; 2025, Kovaleva O.V., Rashidova M.A., Sinyov V.V., Malashenko O.S., Gratchev A.N.Copyright ©; 2025, Ковалева О.В., Рашидова М.А., Синев В.В., Малашенко О.С., Грачев А.Н.2025Kovaleva O.V., Rashidova M.A., Sinyov V.V., Malashenko O.S., Gratchev A.N.Ковалева О.В., Рашидова М.А., Синев В.В., Малашенко О.С., Грачев А.Н.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/755

The study of the role of the immune system in tumor progression has been ongoing for over a century, starting with Paul Ehrlich’s hypothesis on its role in limiting the development of oncological diseases. The development of cancer immunology has confirmed this concept and identified mechanisms of complex interactions between immune system cells and both foreign agents and transformed cells within the organism. Macrophages, natural killers, and T-lymphocytes play key roles in destroying tumor cells. Among them, special attention is given to tumor-associated macrophages. Tumor cells can modulate macrophage activity, transforming them into cells with immunosuppressive properties that promote angiogenesis and extracellular matrix remodeling. As a result, the largest population of tumor-associated macrophages consists of cells with an anti-inflammatory/pro-tumor phenotype (M2).Macrophages with an anti-inflammatory phenotype (M1) are characterized by the production of pro-inflammatory cytokines, reactive oxygen species, and strong cytotoxic activity. They can directly or indirectly destroy tumor cells by involving other immune cells. Traditionally, the cytotoxic activity of macrophages is considered an important mechanism in limiting tumor growth, but in some cases, it is insufficient for effective tumor control. Recent data suggest that tumor cells can develop defense mechanisms against macrophage cytotoxicity and acquire the ability to overcome it. Moreover, tumor cells resulting from interaction with cytotoxic macrophages possess other properties that provide growth advantages.This review is dedicated to describing a new pro-tumor function of M1 macrophages, traditionally considered anti-tumor.

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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