<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">inovmed</journal-id><journal-title-group><journal-title xml:lang="ru">Инновационная медицина Кубани</journal-title><trans-title-group xml:lang="en"><trans-title>Innovative Medicine of Kuban</trans-title></trans-title-group></journal-title-group><issn pub-type="epub">2541-9897</issn><publisher><publisher-name>Scientific Research Institute – Ochapovsky Regional Clinical Hospital No. 1</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.35401/2541-9897-2022-25-3-20-28</article-id><article-id custom-type="elpub" pub-id-type="custom">inovmed-569</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ СТАТЬИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL ARTICLES</subject></subj-group></article-categories><title-group><article-title>Сравнительный анализ некоторых иммунологических параметров в зависимости от локализации опухоли в правой и левой половинах ободочной кишки</article-title><trans-title-group xml:lang="en"><trans-title>Comparative analysis of some immunological parameters depending on the tumor location on the right and left sides of colon</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3061-6108</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кит</surname><given-names>О. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Kit</surname><given-names>O. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кит Олег Иванович - доктор медицинских наук, профессор, академик РАН, генеральный директор.</p><p>Ростов-на-Дону</p></bio><bio xml:lang="en"><p>Oleg I. Kit - Dr. Sci. (Med.), Professor, Academician of the Russian Academy of Sciences, General Director.</p><p>Rostov-on-Don</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3561-098X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Дженкова</surname><given-names>Е. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Dzhenkova</surname><given-names>E. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Дженкова Елена Алексеевна - доктор биологических наук, доцент, ученый секретарь ученого совета.</p><p>Ростов-на-Дону</p></bio><bio xml:lang="en"><p>Elena A. Dzhenkova - Dr. Sci. (Bio.), Associate Professor, Scientific Secretary of the Academic Council.</p><p>Rostov-on-Don</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0328-9714</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Мирзоян</surname><given-names>Э. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Mirzoyan</surname><given-names>E. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Мирзоян Эллада Арменовна - аспирант.</p><p>344037, Ростов-на-Дону, ул. 14-я линия, 63</p></bio><bio xml:lang="en"><p>Ellada A. Mirzoyan - Postgraduate Student.</p><p>63, 14th str., Rostov-on-Don, 344037</p><p> </p></bio><email xlink:type="simple">ellada.mirzoyan@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-0874-5261</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сагакянц</surname><given-names>А. Б.</given-names></name><name name-style="western" xml:lang="en"><surname>Sagakyants</surname><given-names>A. B.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Сагакянц Александр Борисович - кандидат биологических наук, доцент, заведующий лабораторией иммунофенотипирования опухолей.</p><p>Ростов-на-Дону</p></bio><bio xml:lang="en"><p>Alexander B. Sagakyants - Cand. Sci. (Bio.), Associate Professor, Head of Laboratory of Immunophenotyping of Tumors.</p><p>Rostov-on-Don</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1410-122X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Златник</surname><given-names>Е. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Zlatnik</surname><given-names>E. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Златник Елена Юрьевна - доктор медицинских наук, профессор, главный научный сотрудник лаборатории иммунофенотипирования опухолей.</p><p>Ростов-на-Дону</p></bio><bio xml:lang="en"><p>Elena Yu. Zlatnik - Dr. Sci. (Med.), Professor, Chief researcher, Laboratory of Immunophenotyping of Tumors.</p><p>Rostov-on-Don</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8522-1026</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Бондаренко</surname><given-names>Е. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Bondarenko</surname><given-names>E. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Бондаренко Елена Сергеевна - младший научный сотрудник лаборатории иммунофенотипирования опухолей.</p><p>Ростов-на-Дону</p></bio><bio xml:lang="en"><p>Elena S. Bondarenko - Junior researcher, Laboratory of Immunophenotyping of Tumors.</p><p>Rostov-on-Don</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6496-9641</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Новикова</surname><given-names>И. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Novikova</surname><given-names>I. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Новикова Инна Арнольдовна - кандидат медицинских наук, заместитель генерального директора по науке.</p><p>Ростов-на-Дону</p></bio><bio xml:lang="en"><p>Inna A. Novikova - Cand. Sci. (Med.), Deputy General Director for Science.</p><p>Rostov-on-Don</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7328-8074</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Маслов</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Maslov</surname><given-names>A. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Маслов Андрей Александрович - доктор медицинских наук, профессор, главный врач.</p><p>Ростов-на-Дону</p></bio><bio xml:lang="en"><p>Andrey A. Maslov - Dr. Sci. (Med.), Professor, Chief Physician.</p><p>Rostov-onDon</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Национальный медицинский исследовательский центр онкологии</institution><country>Россия</country></aff><aff xml:lang="en"><institution>National Medical Research Centre for Oncology</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2022</year></pub-date><pub-date pub-type="epub"><day>30</day><month>09</month><year>2022</year></pub-date><volume>0</volume><issue>3</issue><fpage>20</fpage><lpage>28</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Кит О.И., Дженкова Е.А., Мирзоян Э.А., Сагакянц А.Б., Златник Е.Ю., Бондаренко Е.С., Новикова И.А., Маслов А.А., 2022</copyright-statement><copyright-year>2022</copyright-year><copyright-holder xml:lang="ru">Кит О.И., Дженкова Е.А., Мирзоян Э.А., Сагакянц А.Б., Златник Е.Ю., Бондаренко Е.С., Новикова И.А., Маслов А.А.</copyright-holder><copyright-holder xml:lang="en">Kit O.I., Dzhenkova E.A., Mirzoyan E.A., Sagakyants A.B., Zlatnik E.Y., Bondarenko E.S., Novikova I.A., Maslov A.A.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.innovmedkub.ru/jour/article/view/569">https://www.innovmedkub.ru/jour/article/view/569</self-uri><abstract><sec><title>Актуальность</title><p>Актуальность: На сегодняшний день колоректальный рак – актуальная проблема в онкологии. В последнее время интерес специалистов прикован к сравнительному анализу различий клинического течения заболеваний злокачественными опухолями ободочной кишки, в частности, ее проксимального и дистального отделов. Как известно, данные отделы имеют не только различные эмбриогенезы, источники кровоснабжения, но и несходные клиническое течение и популяционно-эпидемиологические характеристики. Вопрос о наличии отличительных иммунологических особенностей между опухолями ободочной кишки, в зависимости от локализации, остается открытым.</p></sec><sec><title>Цель исследования</title><p>Цель исследования: Сравнительный анализ локального субпопуляционного состава иммунокомпетентных клеток, а также оценка количества клеток с фенотипом CD45+/-, которые экспрессируют толл-подобные рецепторы (Toll-like receptors (TLRs) в зависимости от локализации опухоли в правой и левой половинах ободочной кишки.</p></sec><sec><title>Материал и методы</title><p>Материал и методы: В работу включены 50 пациентов с верифицированным раком ободочной кишки. Бóльшую часть составили больные женского пола – 26 (52%), средний возраст 67 ± 0,4 лет. 50% выборки – пациенты, у которых выявлена II стадия. Больные были разделены на 2 равные группы, в зависимости от локализации опухоли (правая или левая половина ободочной кишки). Всем пациентам на начальном этапе выполнено стандартное оперативное вмешательство. Полученный материал был использован для последующих исследований: из фрагмента ткани опухолей, перифокальной зоны (1–3 см от опухоли) была получена клеточная суспензия, которую обрабатывали при помощи панели антител (Becton Dickinson, USA) для выявления основных субпопуляций лейкоцитов и лимфоцитов. Также была определена экспрессия TLRs (2, 3, 4, 8, 9) на клетках с фенотипом CD45+, CD45- с использованием проточного цитометра BD FACSCanto (Becton Dickinson, USA). Статистическая обработка данных проводилась с использованием пакета STATISTICA 13.3 (StatSoft Inc., США).</p></sec><sec><title>Результаты</title><p>Результаты: При проведении сравнительного анализ ряда иммунологических параметров, в зависимости от локализации опухоли в правой и левой половинах ободочной кишки, были получены следующие данные:</p></sec><sec><title>Заключение</title><p>Заключение: Выявленные особенности локального субпопуляционного состава иммунокомпетентных клеток при раке ободочной кишки, в зависимости от локализации опухоли, а также данные о количественном клеточном составе клеток с фенотипом CD45+/-, экспрессирующих TLRs, могут быть использованы в прогнозе течения заболевания, а также при выборе тактики лечения.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Background</title><p>Background: Colorectal cancer is now an urgent problem in oncology. Recently, specialists have been interested in a comparative analysis of differences in the clinical course of malignant tumors in the proximal and distal colon. The sections differ not only in their embryogenesis and sources of blood supply, but also in the clinical course and population and epidemiological characteristics. The issue of distinctive immunological characteristics of tumors of the colon depending on the location remains open.</p></sec><sec><title>Objective</title><p>Objective: A comparative analysis of local subpopulations of immunocompetent cells and an assessment of number of cells with the CD45+/- phenotype expressing toll-like receptors (TLRs) depending on the tumor location on the right or left sides of the colon.</p></sec><sec><title>Material and methods</title><p>Material and methods: The study included 50 patients with verified colon cancer. The majority of patients were females – 26 (52%), aged 67 ± 0.4 years, and 50% of patients with stage II disease. Depending on the tumor location (the right or left sides of the colon), the patients were divided into 2 groups of 25 people each. All patients underwent standard surgery at the initial stage. The obtained material was used for subsequent studies: a cell suspension was obtained from a tumor tissue fragment, the perifocal zone (1–3 cm from the tumor) which was processed using an antibody panel (Becton Dickinson, USA) to identify the main subpopulations of leukocytes and lymphocytes. Expression of TLRs (2, 3, 4, 8, 9) on CD45+, CD45- cell populations was also determined using the BD FACSCanto flow cytometer (Becton Dickinson, USA). Statistical processing of the results was performed using the STATISTICA 13.3 package (StatSoft Inc., USA).</p></sec><sec><title>Results</title><p>Results: A comparative analysis of immunological parameters, depending on the tumor location on the right or left sides of the colon, showed:</p></sec><sec><title>Conclusion</title><p>Conclusion: The revealed characteristics of the local subpopulations of immunocompetent cells and the numbers of CD45+/- cells expressing TLRs depending on the tumor location on the right or left sides of the colon can serve as a prognosis of the disease clinical course and the choice of further treatment tactics.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>рак ободочной кишки</kwd><kwd>локальный клеточный иммунитет</kwd><kwd>Toll-подобные рецепторы</kwd></kwd-group><kwd-group xml:lang="en"><kwd>colon cancer</kwd><kwd>local cellular immunity</kwd><kwd>toll-like receptors</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Работа выполнена в рамках государственного задания по теме «Разработка прогностических и предиктивных алгоритмов на основе выявления новых иммунологических и молекулярно-генетических характеристик злокачественных опухолей и их микроокружения», рег. №121031100251-9</funding-statement><funding-statement xml:lang="en">The work was performed as part of the state assignment on the topic «Development of prognostic and predictive algorithms based on the identification of new immunological and molecular genetic characteristics of malignant tumors and their microenvironment», reg. No. 121031100251-9</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Кит О.И. Проблема колоректального рака в начале ХХI века: достижения и перспективы. Российский журнал Гастроэнтерологии, Гепатологии, Колопроктологии. 2013;3(23):65–71.</mixed-citation><mixed-citation xml:lang="en">Kit OI. Issue of colorectal cancer at the beginning of 21 century: achievements and prospects. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2013;3(23):65–71. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Кит О.И., Дженкова Е.А., Мирзоян Э.А. и др. Молекулярно-генетическая классификация подтипов колоректального рака: современное состояние проблемы. Южно-Российский онкологический журнал. 2021;2(2):50–56. https://doi.org/10.37748/2686-9039-2021-2-2-6</mixed-citation><mixed-citation xml:lang="en">Kit OI, Dzhenkova EA, Mirzoyan EA, et al. Molecular genetic classification of colorectal cancer subtypes: current state of the problem. South Russian Journal of Cancer. 2021;2(2):50–56. (In Russ.). https://doi.org/10.37748/2686-9039-2021-2-2-6</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Мараткызы М., Кабилдина Н.А., Бейсенаева А.Р. и др. Эпидемиологические аспекты колоректального рака. Медицина и экология. 2020;2(95):15–20.</mixed-citation><mixed-citation xml:lang="en">Maratkyzy M, Kabildina NA, Beisenayeva AR, et al. Epidemiological aspects of colorectal cancer. Medicine and ecology. 2020;2(95):15–20. (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Каприн А.Д., Старинский В.В., Шахзадова А.О. Злокачественные новообразования в России в 2020 году (заболеваемость и смертность). М.: МНИОИ им. П.А. Герцена − филиал ФГБУ «НМИЦ радиологии» Минздрава России; 2021:252.</mixed-citation><mixed-citation xml:lang="en">Kaprin AD, Starinsky VV, Shakhzadova AO. Malignant neoplasms in Russia in 2020 (morbidity and mortality). Moscow: National Medical Research Center of Radiology of the Russian Ministry of Health; 2021:252. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Кит О.И., Дженкова Е.А., Мирзоян Э.А. и др. Особенности локального клеточного иммунитета при раке ободочной кишки в зависимости от локализации опухолевого процесса. Современные проблемы науки и образования. 2022;3. https://doi.org/10.17513/spno.31695</mixed-citation><mixed-citation xml:lang="en">Kit OI, Dzhenkova EA, Mirzoyan EA, et al. Characteristics of local cellular immunity in colon cancer depending on tumor location. Modern Problems of Science and Education. 2022;3. (In Russ.). https://doi.org/10.17513/spno.31695</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Федянин М.Ю., Трякин А.А., Тюляндин С.А. Локализация первичной опухоли толстой кишки: есть ли принципиальные отличия? Тазовая хирургия и онкология. 2017;7(3):35−48. https://doi.org/10.17650/2220-3478-2017-7-3-35-48</mixed-citation><mixed-citation xml:lang="en">Fedyanin MYu, Tryakin AA, Tjulandin SA. Localization of the primary tumor of the colon: are there essential differences? Pelvic Surgery and Oncology. 2017;7(3):35−48. (In Russ.). https://doi.org/10.17650/2220-3478-2017-7-3-35-48</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Benedix F, Schmidt U, Mroczkowski P, et al. Colon carcinoma – classification into right and left sided cancer or according to colonic subsite? Analysis of 29,568 patients. Eur J Surg Oncolс. 2011;37(2):134–139. PMID: 21193285. https://doi.org/10.1016/j.ejso.2010.12.004</mixed-citation><mixed-citation xml:lang="en">Benedix F, Schmidt U, Mroczkowski P, et al. Colon carcinoma – classification into right and left sided cancer or according to colonic subsite? Analysis of 29,568 patients. Eur J Surg Oncolс. 2011;37(2):134–139. PMID: 21193285. https://doi.org/10.1016/j.ejso.2010.12.004</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Давыдов М.И., Ганцев Ш.Х. Онкология: учебник. М.: ГЭОТАР-Медиа; 2020:920.</mixed-citation><mixed-citation xml:lang="en">Davydov MI, Gantsev ShKh. Oncology: textbook. Moscow: GEOTAR-Media; 2020:920. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Sears CL, Geis AL, Housseau F. Bacteroides fragilis subverts mucosal biology: from symbiont to colon carcinogenesis. J Clin Invest. 2014;124(10):4166–4172. PMID: 25105360. PMCID: PMC4191034. https://doi.org/10.1172/JCI72334</mixed-citation><mixed-citation xml:lang="en">Sears CL, Geis AL, Housseau F. Bacteroides fragilis subverts mucosal biology: from symbiont to colon carcinogenesis. J Clin Invest. 2014;124(10):4166–4172. PMID: 25105360. PMCID: PMC4191034. https://doi.org/10.1172/JCI72334</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">LaPointe LC, Dunne R, Brown GS, et al. Map of differential transcript expression in the normal human large intestine. Physiol Genomics. 2008;33(1):50–64. PMID: 18056783. https://doi.org/10.1152/physiolgenomics.00185.2006</mixed-citation><mixed-citation xml:lang="en">LaPointe LC, Dunne R, Brown GS, et al. Map of differential transcript expression in the normal human large intestine. Physiol Genomics. 2008;33(1):50–64. PMID: 18056783. https://doi.org/10.1152/physiolgenomics.00185.2006</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Сагакянц А.Б. Объединенный иммунологический форум: современные направления развития фундаментальной и прикладной онкоиммунологии (Новосибирск, 2019). Южнороссийский онкологический журнал. 2020;1(2):36–45. https://doi.org/10.37748/2687-0533-2020-1-2-5</mixed-citation><mixed-citation xml:lang="en">Sagakyants AB. United immunological forum: current trends in the development of fundamental and applied oncoimmunology (Novosibirsk, 2019). South Russian Journal of Cancer. 2020;1(2):36– 45. (In Russ.). https://doi.org/10.37748/2687-0533-2020-1-2-5</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Schreiber RD. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011;331:1565–1570. PMID: 21436444. https://doi.org/10.1126/science.1203486</mixed-citation><mixed-citation xml:lang="en">Schreiber RD. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011;331:1565–1570. PMID: 21436444. https://doi.org/10.1126/science.1203486</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Väyrynen JP, Tuomisto A, Klintrup K, et al. Detailed analysis of inflammatory cell infiltration in colorectal cancer. British Journal of Cancer. 2013;109:1839–1847. PMID: 24008661. PMCID: PMC3790164. https://doi.org/10.1038/bjc.2013.508</mixed-citation><mixed-citation xml:lang="en">Väyrynen JP, Tuomisto A, Klintrup K, et al. Detailed analysis of inflammatory cell infiltration in colorectal cancer. British Journal of Cancer. 2013;109:1839–1847. PMID: 24008661. PMCID: PMC3790164. https://doi.org/10.1038/bjc.2013.508</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Кит О.И., Франциянц Е.М., Никипелова Е.А. и др. Изменения маркеров пролиферации, неоангиогенеза и системы активации плазминогена в ткани рака прямой кишки. Экспериментальная и клиническая гастроэнтерология. 2015;114(2):40–45.</mixed-citation><mixed-citation xml:lang="en">Kit OI, Frantsiyants EM, Nikipelova EA, et al. Changes in markers of proliferation, neoangiogenesis and plasminogen activation system in rectal cancer tissue. Experimental and Clinical Gastroenterology. 2015;114(2):40–45. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Tabiasco J, Devêvre E, Rufer N, et al. Human effector CD8+T lymphocytes express TLR3 as a functional coreceptor. Journal of immunology. 2006;177(12):8708–8713. PMID: 17142772. https://doi.org/10.4049/jimmunol.177.12.8708</mixed-citation><mixed-citation xml:lang="en">Tabiasco J, Devêvre E, Rufer N, et al. Human effector CD8+T lymphocytes express TLR3 as a functional coreceptor. Journal of immunology. 2006;177(12):8708–8713. PMID: 17142772. https://doi.org/10.4049/jimmunol.177.12.8708</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Li TT, Ogino S, Qian ZR. Toll-like receptor signaling in colorectal cancer: carcinogenesis to cancer therapy. World journal of gastroenterology. 2014;20(47):17699–17708. PMID: 25548469. PMCID: PMC4273121. https://doi.org/10.3748/wjg.v20.i47.17699</mixed-citation><mixed-citation xml:lang="en">Li TT, Ogino S, Qian ZR. Toll-like receptor signaling in colorectal cancer: carcinogenesis to cancer therapy. World journal of gastroenterology. 2014;20(47):17699–17708. PMID: 25548469. PMCID: PMC4273121. https://doi.org/10.3748/wjg.v20.i47.17699</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Свитич О.А., Филина А.Б., Давыдова Н.В. и др. Роль факторов врожденного иммунитета в процессе опухолеобразования. Медицинская иммунология. 2018;20(2):151–162. https://doi.org/10.15789/1563-0625-2018-2-151-162</mixed-citation><mixed-citation xml:lang="en">Svitich OA, Filina AB, Davydova NV, et al. The role of innate immunity factors in tumorigenesis process. Medical Immunology (Russia). 2018;20(2):151–162. (In Russ.) https://doi.org/10.15789/1563-0625-2018-2-151-162</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Pages F, Galon J, Fridman WH. The essential role of the in situ immune reaction in human colorectal cancer. Jornal of Leukocyte Biology. 2008;84(4):981–987. PMID: 18559950. https://doi.org/10.1189/jlb.1107773</mixed-citation><mixed-citation xml:lang="en">Pages F, Galon J, Fridman WH. The essential role of the in situ immune reaction in human colorectal cancer. Jornal of Leukocyte Biology. 2008;84(4):981–987. PMID: 18559950. https://doi.org/10.1189/jlb.1107773</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Grizzi F, Bianchi P, Malesci A, et al. Prognostic value of innate and adaptive immunity in colorectal cancer. World Journal of Gastroenterology. 2013;19(2):174–184. PMID: 23345940. PMCID: PMC3547568. https://doi.org/10.3748/wjg.v19.i2.174</mixed-citation><mixed-citation xml:lang="en">Grizzi F, Bianchi P, Malesci A, et al. Prognostic value of innate and adaptive immunity in colorectal cancer. World Journal of Gastroenterology. 2013;19(2):174–184. PMID: 23345940. PMCID: PMC3547568. https://doi.org/10.3748/wjg.v19.i2.174</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Mei Z, Liu Y, Liu C, et al. Tumor-infiltrating inflammation and prornosis in colorectal cancer: systematic review and meta-analysis. British Journal of Cancer. 2014;110(6):1595–1605. PMID: 24504370. PMCID: PMC3960618. https://doi.org/10.1038/bjc.2014.46</mixed-citation><mixed-citation xml:lang="en">Mei Z, Liu Y, Liu C, et al. Tumor-infiltrating inflammation and prornosis in colorectal cancer: systematic review and meta-analysis. British Journal of Cancer. 2014;110(6):1595–1605. PMID: 24504370. PMCID: PMC3960618. https://doi.org/10.1038/bjc.2014.46</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Chiba T, Ohtani H, Mizoi T, et al. Intraepithelial CD8+ T-cell-count becomes a prognostic factor after a longer followup period in human colorectal carcinoma: possible association with suppression of micrometastasis. British Journal of Cancer. 2004;91(9):1711–1717. PMID: 15494715. PMCID: PMC2410024. https://doi.org/10.1038/sj.bjc.6602201</mixed-citation><mixed-citation xml:lang="en">Chiba T, Ohtani H, Mizoi T, et al. Intraepithelial CD8+ T-cell-count becomes a prognostic factor after a longer followup period in human colorectal carcinoma: possible association with suppression of micrometastasis. British Journal of Cancer. 2004;91(9):1711–1717. PMID: 15494715. PMCID: PMC2410024. https://doi.org/10.1038/sj.bjc.6602201</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Nosho K, Baba Y, Tanaka N, et al. Tumour-infiltrating T-cell subsets, molecular changes in colorectal cancer, and prognosis: cohort study and literature review. Journal of Pathology. 2010;222(4):350–366. PMID: 20927778. PMCID: PMC3033700. https://doi.org/10.1002/path.2774</mixed-citation><mixed-citation xml:lang="en">Nosho K, Baba Y, Tanaka N, et al. Tumour-infiltrating T-cell subsets, molecular changes in colorectal cancer, and prognosis: cohort study and literature review. Journal of Pathology. 2010;222(4):350–366. PMID: 20927778. PMCID: PMC3033700. https://doi.org/10.1002/path.2774</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Masayuki F, Yasmin H, Daisy C, et al. Innate immune signaling by Toll-like receptor-4 (TLR4) shapes the inflammatory microenvironment in colitisassociated tumors. Inflammatory Bowel Diseases. 2009;15(7):997–1006. PMID: 19229991. PMCID: PMC2712657. https://doi.org/10.1002/ibd.20880</mixed-citation><mixed-citation xml:lang="en">Masayuki F, Yasmin H, Daisy C, et al. Innate immune signaling by Toll-like receptor-4 (TLR4) shapes the inflammatory microenvironment in colitisassociated tumors. Inflammatory Bowel Diseases. 2009;15(7):997–1006. PMID: 19229991. PMCID: PMC2712657. https://doi.org/10.1002/ibd.20880</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Garaude J, Kent A, van Rooijen N, et al. Simultaneous targeting of toll- and nod-like receptors induces effective tumorspecific immune responses. Science Translational Medicine. 2012;4(120):120ra16. PMID: 22323829. https://doi.org/10.1126/scitranslmed.3002868</mixed-citation><mixed-citation xml:lang="en">Garaude J, Kent A, van Rooijen N, et al. Simultaneous targeting of toll- and nod-like receptors induces effective tumorspecific immune responses. Science Translational Medicine. 2012;4(120):120ra16. PMID: 22323829. https://doi.org/10.1126/scitranslmed.3002868</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Wang EL, Qian ZR, Nakasono M, et al. High expression of Toll-like receptor 4/myeloid differentiation factor 88 signals correlates with poor prognosis in colorectal cancer. British journal of cancer. 2010;102(5):908–915. PMID: 20145615. PMCID: PMC2833250. https://doi.org/10.1038/sj.bjc.6605558</mixed-citation><mixed-citation xml:lang="en">Wang EL, Qian ZR, Nakasono M, et al. High expression of Toll-like receptor 4/myeloid differentiation factor 88 signals correlates with poor prognosis in colorectal cancer. British journal of cancer. 2010;102(5):908–915. PMID: 20145615. PMCID: PMC2833250. https://doi.org/10.1038/sj.bjc.6605558</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Kantola T, Klintrup K, Väyrynen JP, et al. Stage-dependent alterations of the serum cytokine pattern in colorectal carcinoma. British journal of cancer. 2012;107(10):1729–1736. PMID: 23059742. PMCID: PMC3493870. https://doi.org/10.1038/bjc.2012.456</mixed-citation><mixed-citation xml:lang="en">Kantola T, Klintrup K, Väyrynen JP, et al. Stage-dependent alterations of the serum cytokine pattern in colorectal carcinoma. British journal of cancer. 2012;107(10):1729–1736. PMID: 23059742. PMCID: PMC3493870. https://doi.org/10.1038/bjc.2012.456</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Tye H, Jenkins BJ. Tying the knot between cytokine and toll-like receptor signaling in gastrointestinal tract cancers. Cancer science. 2013;104(9):1139–1145. PMID: 23710764. PMCID: PMC7656558. https://doi.org/10.1111/cas.12205</mixed-citation><mixed-citation xml:lang="en">Tye H, Jenkins BJ. Tying the knot between cytokine and toll-like receptor signaling in gastrointestinal tract cancers. Cancer science. 2013;104(9):1139–1145. PMID: 23710764. PMCID: PMC7656558. https://doi.org/10.1111/cas.12205</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">O’Leary DP, Bhatt L, Woolley JF, et al. TLR-4 signalling accelerates colon cancer cell adhesion via NF-κB mediated transcriptional up-regulation of Nox-1. PLoS One. 2012;7(10):e44176. PMID: 23071493. PMCID: PMC3469572. https://doi.org/10.1371/journal.pone.0044176</mixed-citation><mixed-citation xml:lang="en">O’Leary DP, Bhatt L, Woolley JF, et al. TLR-4 signalling accelerates colon cancer cell adhesion via NF-κB mediated transcriptional up-regulation of Nox-1. PLoS One. 2012;7(10):e44176. PMID: 23071493. PMCID: PMC3469572. https://doi.org/10.1371/journal.pone.0044176</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Rahman AH, Taylor DK, Turka LA. The contribution of direct TLR signaling to T cell responses. Immunologic research. 2009;45(1):25–36. PMID: 19597998. PMCID: PMC4486050. https://doi.org/10.1007/s12026-009-8113-x</mixed-citation><mixed-citation xml:lang="en">Rahman AH, Taylor DK, Turka LA. The contribution of direct TLR signaling to T cell responses. Immunologic research. 2009;45(1):25–36. PMID: 19597998. PMCID: PMC4486050. https://doi.org/10.1007/s12026-009-8113-x</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
