Almanac of Clinical MedicineAlmanac of Clinical MedicineАльманах клинической медицины2072-05052587-9294Moscow Regional Research and Clinical Institute (MONIKI)165510.18786/2072-0505-2022-50-008REVIEW ARTICLEОБЗОРReview ArticleMacrophage cytotoxic activity and its role in the tumor pathogenesisЦитотоксическая активность макрофагов и ее роль в патогенезе опухолейhttps://orcid.org/0000-0001-6132-9924KovalevaOlga V.КовалеваОльга Владимировна
Russian Federation

PhD (in Biol.), Senior Research Fellow, Laboratory of Regulation of Cellular and Viral Oncogenes, Research Institute of Carcinogenesis

канд. биол. наук, ст. науч. сотр. лаборатории регуляции клеточных и вирусных онкогенов Научно-исследовательского института канцерогенеза

ovkovaleva@gmail.comhttps://orcid.org/0000-0003-2312-5546PodlesnayaPolina A.ПодлеснаяПолина Алексеевна
Russian Federation

Research Assistant, Laboratory of Tumor Stromal Cells Biology, Research Institute of Carcinogenesis

лаборант-исследователь лаборатории биологии стромальных клеток опухолей Научно-исследовательского института канцерогенеза

polina.pod@yandex.ruhttps://orcid.org/0000-0003-2137-1866GratchevAlexei N.ГрачевАлексей Николаевич
Russian Federation

Doctor of Biol. Sci., Head of Laboratory of Tumor Stromal Cells Biology

д-р биол. наук, заведующий лабораторией биологии стромальных клеток опухолей Научно-исследовательского института канцерогенеза

alexei.gratchev@gmail.comN.N. Blokhin National Medical Research Center of OncologyФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России050420222804202250113202103202230032022Copyright ©; 2022, Kovaleva O.V., Podlesnaya P.A., Gratchev A.N.Copyright ©; 2022, Ковалева О.В., Подлесная П.А., Грачев А.Н.2022Kovaleva O.V., Podlesnaya P.A., Gratchev A.N.Ковалева О.В., Подлесная П.А., Грачев А.Н.https://creativecommons.org/licenses/by-nc/4.0https://almclinmed.ru/jour/article/view/1655

Macrophages, natural killers and T cells play the central role in tumor cells destruction. The purpose of this review is to summarize the state-of-the-art perspectives of the interplay between tumor cells and tumor stroma leading both to the formation of a macrophage population incapable of effective antitumor activity and to the selection of tumor cells resistant to macrophage cytotoxicity.

Macrophages are highly versatile cells that can both stimulate the inflammatory response (type 1 macrophages, M1) and suppress it (type 2 macrophages, M2). Tumor-associated macrophages (TAMs) are considered the main regulator of the antitumor immune response and usually have anti-inflammatory properties, that is, they belong to M2 type. Tumor cells are able to affect macrophages, "reprogramming" them to perform an immunosuppressive function. In addition, TAMs stimulate angiogenesis and remodelling of the extracellular matrix necessary for metastasis.

Recently, more and more studies have been published describing a mixed TAMs phenotype with characteristics of both M2 and M1. M1 is characterized by production of pro-inflammatory cytokines, reactive oxygen species, bactericidal and cytotoxic activity. M1 can destroy tumor cells both directly and indirectly by attracting other cells. Despite the mechanisms of direct cytotoxic activity are quite variable, their effectiveness is largely dependent on the properties of a particular tumor. The cytotoxic activity of macrophages is a powerful factor that inhibits tumor initiation and progression. However, in some cases, it is not sufficient to control the tumor process. Activation of the cytotoxic activity of TAMs is one of the strategies to use macrophages for cancer treatment.

Understanding the mechanisms of macrophage cytotoxic activity and specific patterns of its manifestation in a tumor environment is of critical importance for better effectiveness of existing cancer treatments and development of promising methods for tumor immunotherapy.

Центральную роль в уничтожении опухолевых клеток играют макрофаги, натуральные киллеры и Т-клетки. Цeль данного обзора – определить современные взгляды на механизмы взаимодействия опухолевых клеток и опухолевой стромы, приводящие как к формированию популяции макрофагов, неспособных к эффективной противоопухолевой активности, так и к отбору опухолевых клеток, устойчивых к цитотоксичности макрофагов.

Макрофаги – весьма разносторонние клетки, способные не только стимулировать воспалительную реакцию (макрофаги 1-го типа – М1), но и подавлять ее (макрофаги 2-го типа – М2). Макрофаги, ассоциированные с опухолью (МАО), считаются основным регулятором противоопухолевого иммунного ответа и, как правило, обладают противовоспалительными свойствами, то есть относятся к типу М2. Опухолевые клетки способны влиять на макрофаги, «перепрограммируя» их на выполнение иммуносупрессорной функции. МАО также стимулируют ангиогенез и перестройку внеклеточного матрикса, необходимую для метастазирования.

В последнее время появляется все больше работ, в которых описаны МАО смешанного фенотипа, обладающие характеристиками как М2, так и М1. Для М1 характерна продукция провоспалительных цитокинов, активных форм кислорода, бактерицидная и цитотоксическая активность. М1 могут уничтожать опухолевые клетки прямым или косвенным способом, путем привлечения других клеток. Несмотря на то что механизмы прямой цитотоксической активности достаточно вариативны, их эффективность в значительной степени зависит от свойств конкретной опухоли. Цитотоксическая активность макрофагов является мощным фактором, сдерживающим инициацию и прогрессию опухоли, однако в ряде случаев ее недостаточно для контроля опухолевого процесса. Активация цитотоксической активности МАО лежит в основе одной из стратегий использования макрофагов при лечении онкологических заболеваний.

Понимание механизмов цитотоксической активности макрофагов и особенностей ее проявления в условиях опухолевого окружения критически важно для повышения эффективности существующих методов лечения онкологических заболеваний и разработки перспективных методов иммунотерапии опухолей.

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