mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-2018-2-151-162mimmun-1477Research ArticleОБЗОРЫREVIEWSРОЛЬ ФАКТОРОВ ВРОЖДЕННОГО ИММУНИТЕТА В ПРОЦЕССЕ ОПУХОЛЕОБРАЗОВАНИЯTHE ROLE OF INNATE IMMUNITY FACTORS IN TUMORIGENESIS PROCESSСвитичО. А.SvitichO. A.

д.м.н., член-корр. РАН, заведующая лабораторией молекулярной иммунологии

105064, Россия, Москва, Малый Казенный переулок, 5а. Тел.: 8 (926)148-83-22

PhD, MD (Medicine), Corresponding Member, Russian Academy of Sciences, Head, Laboratory of Molecular Immunology

Malii Kasennii lane, 5a. Phone: 7 (926) 148-83-22

svitichoa@yandex.ruФилинаА. Б.FilinaA. B.

младший научный сотрудник лаборатории молекулярной иммунологии

Junior Research Associate, Laboratory of Molecular Immunology

ДавыдоваН. В.DavydovaN. V.

к.м.н., доцент кафедры микробиологии, вирусологии и иммунологии

PhD (Medicine), Associate Professor, Department of Microbiology, Virology and Immunology

ГанковскаяЛ. В.GankovskayaL. V.

д.м.н., профессор, заведующая кафедрой иммунологии

PhD, MD (Medicine), Professor, Head, Department of Immunology

ЗверевВ. В.ZverevV. V.

д.б.н., профессор, академик РАН, директор

PhD, MD (Biology), Professor, Full Member, Russian Academy of Sciences, Director

ФГБНУ «Научно-исследовательский институт вакцин и сывороток имени И.И. Мечникова»; ФГАОУ ВО «Первый Московский государственный медицинский университет имени И.М. Сеченова» Министерства здравоохранения РФ; ФГБОУ ВО «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова»РоссияI. Mechnikov Research Institute of Vaccines and Sera; First Moscow I.M. Sechenov State Medical University; Russian National Research N.I. Pirogov Medical UniversityRussian FederationФГБНУ «Научно-исследовательский институт вакцин и сывороток имени И.И. Мечникова»; ФГАОУ ВО «Первый Московский государственный медицинский университет имени И.М. Сеченова» Министерства здравоохранения РФРоссияI. Mechnikov Research Institute of Vaccines and Sera; First Moscow I.M. Sechenov State Medical UniversityRussian FederationФГАОУ ВО «Первый Московский государственный медицинский университет имени И.М. Сеченова» Министерства здравоохранения РФРоссияFirst Moscow I.M. Sechenov State Medical UniversityRussian FederationФГБОУ ВО «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова»РоссияRussian National Research N.I. Pirogov Medical UniversityRussian Federation201815032018202151162Copyright © Свитич О.А., Филина А.Б., Давыдова Н.В., Ганковская Л.В., Зверев В.В., 20182018Свитич О.А., Филина А.Б., Давыдова Н.В., Ганковская Л.В., Зверев В.В.Svitich O.A., Filina A.B., Davydova N.V., Gankovskaya L.V., Zverev V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/1477

Одной из важнейших теорий канцерогенеза является теория о полиэтиологичности опухолеобразования. Большое место в этой теории отводится роли воспалительного компонента, который реализуется посредством факторов врожденного иммунитета.

К факторам врожденного иммунитета, участвующим в опухолеобразовании, относятся TLRs, хемокины и их рецепторы. Активация TLRs может приводить как к снижению прогрессии онкологического процесса, так и, наоборот, к усилению. Известно, что TLR3, TLR5, TLR7, TLR9 обладают наибольшим противоопухолевым эффектом через DCs-опосредованную активацию Тh1, активацию макрофагов М1-типа и ингибирование Treg. Стимуляция TLR4 и TLR2 обладает опухоль-активирующим эффектом, путем гиперактивации MyD88 и выработки IL-6 и TNFα, однако механизмы до конца не изучены. Помимо TLRs, большое влияние на развитие онкологического процесса оказывают хемокины и их рецепторы. Показано, что CCL2, CCL4, CCL17, CCL22 и CXCL12, выделяемые клетками микроокружения опухоли, активно влияют на хемотаксис опухолевых клеток. Также известно, что CXCR4 и CCR7, экспрессируемые опухолевыми клетками, активируются хемокинами, что ведет к метастазированию. Также показаны ассоциации некоторых полиморфизмов генов TLRs, хемокинов и их рецепторов с развитием опухолевого процесса. Таким образом, на основании литературных данных, можно сделать заключение о том, что TLR и хемокины имеют большое значение при онкогенезе. Дальнейшее изучение влияния факторов врожденного иммунитета на онкогенез имеет больше значение для обоснования новых подходов терапии рака, а также потенциал для создания вакцин против рака. 

The theory of polyetiological tumorigenesis is one of the most important theories of carcinogenesis. A great place in this theory is given to the role of inflammatory component, which is implemented via the factors of innate immunity. I.e., toll-like receptors (TLRs), chemokines and their receptors are related to innate immunity. Activation of TLRs may lead to regress or progression of cancer process. It is known that TLR3, TLR5, TLR7, TLR9 have the greatest anti-tumor effect due to the dendritic cells (DCs)-mediated activation of type I T helpers, activation of M1-type macrophages and Treg inhibition. Stimulation of TLR2 and TLR4 exerts an activating effect upon the tumor, by the MyD88 hyperactivation and secretion of IL-6 and TNFα, but exact mechanisms are not fully understood. In addition to TLRs, chemokines and their receptors have a great influence on the cancer development. It is shown that CCL2, CCL4, CCL17, CCL22 and CXCL12, which are secreted by cancer microenviroment, activate chemotaxis of tumor cells. It is also known that the chemokines activate CXCR4 and CCR7 (expressed by tumor cells) thus leading to metastasis.

It is shown that there is an association between some gene polymorphisms of TLRs’, chemokines and their receptors, and development of cancer.

Thus, we may conclude that the role of TLRs and chemokines is important in oncogenesis. Further study of innate immunity factors influencing tumorigenesis are important for finding new approaches to cancer therapy and new potential vaccines against cancer. 

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The authors declare that there are no conflicts of interest present.