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<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">surgonco</journal-id><journal-title-group><journal-title xml:lang="ru">Креативная хирургия и онкология</journal-title><trans-title-group xml:lang="en"><trans-title>Creative surgery and oncology</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2076-3093</issn><issn pub-type="epub">2307-0501</issn><publisher><publisher-name>Башкирский государственный медицинский университет</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.24060/2076-3093-2019-9-4-266-272</article-id><article-id custom-type="elpub" pub-id-type="custom">surgonco-433</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 ИССЛЕДОВАНИЯ</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>Неолимфогенез и иммуногистохимическое исследование лимфатических узлов при раке молочной железы</article-title><trans-title-group xml:lang="en"><trans-title>Neolymphogenesis and Immunogistogochemical Study of Lymph Nodes in Breast Cancer</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2047-963X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ганцев</surname><given-names>Ш. Х.</given-names></name><name name-style="western" xml:lang="en"><surname>Gantsev</surname><given-names>Sh. Kh.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ганцев Шамиль Ханафиевич — д.м.н., профессор, директор НИИ онкологии, зав. кафедрой онкологии с курсами онкологии и патологической анатомии</p><p>450008, Уфа, ул. Ленина, 3</p></bio><bio xml:lang="en"><p>Gantsev Shamil Khanafievich — Doctor of Medical Sciences, Professor, Director of the Scientific Research Institute of Oncology, Head of the Department of Oncology with Oncology and Anatomical Pathology courses in the Institute of Additional Professional Education</p><p>3 Lenin str., Ufa, 450008</p></bio><email xlink:type="simple">prfg@mail.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/0000-0002-0355-1399</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Рустамханов</surname><given-names>Р. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Rustamkhanov</surname><given-names>R. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Рустамханов Расул Айдарович — ассистент кафедры онкологии с курсами онкологии и патологической анатомии ИДПО</p><p>450008, Уфа, ул. Ленина, 3</p></bio><bio xml:lang="en"><p>Rustamkhanov Rasul Aydarovich — Assistant lecturer of the Department of Oncology with Oncology and Anatomical Pathology courses in the Institute of Additional Professional Education</p><p>3 Lenin str., Ufa, 450008</p></bio><email xlink:type="simple">weather86@mail.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/0000-0001-9721-108X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кзыргалин</surname><given-names>Ш. Р.</given-names></name><name name-style="western" xml:lang="en"><surname>Kzyrgalin</surname><given-names>Sh. R.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кзыргалин Шамиль Римович — к.м.н., доцент кафедры онкологии с курсами онкологии и патологической анатомии ИДПО</p><p>450008, Уфа, ул. Ленина, 3</p></bio><bio xml:lang="en"><p>Kzyrgalin Shamil Rimovich — Candidate of Medical Sciences, Associate Professor of the Department of Oncology with Oncology and Anatomical Pathology courses in the Institute of Additional Professional Education</p><p>3 Lenin str., Ufa, 450008</p></bio><email xlink:type="simple">ufa.shamil@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4069-6594</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Турсуметов</surname><given-names>Д. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Tursumetov</surname><given-names>D. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Турсуметов Давлат Сайтмуратович — к.м.н., доцент кафедры онкологии с курсами онкологии и патологической анатомии ИДПО</p><p>450008, Уфа, ул. Ленина, 3</p></bio><bio xml:lang="en"><p>Tursumetov Davlat Saytmuratovich — Candidate of Medical Sciences, Associate Professor of the Department of Oncology with Oncology and Anatomical Pathology courses in the Institute of Additional Professional Education</p><p>3 Lenin str., Ufa, 450008</p></bio><email xlink:type="simple">ufa.davlat@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Башкирский государственный медицинский университет</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Bashkir State Medical University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2019</year></pub-date><pub-date pub-type="epub"><day>23</day><month>01</month><year>2020</year></pub-date><volume>9</volume><issue>4</issue><fpage>266</fpage><lpage>272</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Ганцев Ш.Х., Рустамханов Р.А., Кзыргалин Ш.Р., Турсуметов Д.С., 2020</copyright-statement><copyright-year>2020</copyright-year><copyright-holder xml:lang="ru">Ганцев Ш.Х., Рустамханов Р.А., Кзыргалин Ш.Р., Турсуметов Д.С.</copyright-holder><copyright-holder xml:lang="en">Gantsev S.K., Rustamkhanov R.A., Kzyrgalin S.R., Tursumetov D.S.</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.surgonco.ru/jour/article/view/433">https://www.surgonco.ru/jour/article/view/433</self-uri><abstract><sec><title>Введение</title><p>Введение. Ранее проведенные нами исследования доказали, что постнатально сформированные лимфатические узлы могут служить источником биологических сигналов, активирующих противоопухолевые реакции иммунитета и подавляющих распространение метастазирующих злокачественных клеток.</p></sec><sec><title>Цель работы</title><p>Цель работы: определение экспрессии CD3, CD20, CD68 в нативных, сторожевых и постнатально индуцированных лимфатических узлах аксиллярной зоны при раке молочной железы.</p></sec><sec><title>Материалы и методы</title><p>Материалы и методы. Исследованию подвергались готовые оцифрованные изображения иммуногистохимической экспрессии фиксированной панели антител CD3, CD20, CD68. Проводили количественную оценку экспрессии методом подсчета экспрессированных клеток в каждом исследованном узле по четырем основным структурно-функциональным зонам.</p></sec><sec><title>Результаты и обсуждение</title><p>Результаты и обсуждение. Результаты сравнительного иммуногистохимического исследования нативных, сторожевых и постнатально индуцированных лимфатических узлов показали, что содержание CD3, CD20, CD68 в различных структурах лимфатических узлов имело принципиальные отличия.</p></sec><sec><title>Выводы 1</title><p>Выводы 1. В постнатально индуцированных лимфатических узлах отчетливо выявлена отличная от нативных и сторожевых лимфатических узлов экспрессия антител к основным иммунокомпетентным клеткам, реализующих в лимфатическом узле ключевые иммунные реакции, что может указывать на повышенный функциональный статус новообразованных лимфоузлов. 2. Проведенное исследование демонстрирует высокий уровень антигенной стимуляции Т- и В-лимфоцитов в ПНИЛУ, а также указывает на возможную роль клеток макрофагального ряда в стимуляции неолимфогенеза и образования новых лимфоузлов. 3. Реализация данного научного проекта позволяет в дальнейших научных изысканиях заложить фундаментальные основы для исследований, посвященных постнатальным индуцированным лимфатическим узлам у онкологических больных.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Background</title><p>Background. Our previous studies have shown that postnatally formed lymph nodes (PNFLN) can serve as a source of biological signals activating antitumour immune reactions and suppressing the spread of metastatic malignant cells.</p></sec><sec><title>Aim</title><p>Aim. To determine the expression of CD3, CD20, CD68 in native, sentinel and postnatally induced lymph nodes of the axillary zone in breast cancer.</p></sec><sec><title>Materials and methods</title><p>Materials and methods. The study involved an analysis of digitalized images of the immunohistochemical expression of a fixed panel of antibodies CD3, CD20, CD68. The expression levels were assessed quantitatively by counting the expressed cells in each studied node for four main structural and functional zones.</p></sec><sec><title>Results and Discussion</title><p>Results and Discussion. The results of a comparative immunohistochemical study of native, sentinel and postnatally induced lymph nodes showed that the content of CD3, CD20, CD68 demonstrates fundamental differences in different lymph node structures.</p></sec><sec><title>Сonclusions 1</title><p>Сonclusions 1. In postnatally induced lymph nodes, compared to native and sentinel lymph nodes, the distinct expression of antibodies to the main immunocompetent cells, which realize key immune responses in the lymph node, can indicate an increased functional status of the newly formed lymph nodes. 2. The study demonstrated a high level of antigenic stimulation of T and B lymphocytes in postnatally induced lymph nodes, as well as indicated a possible role of macrophage cells in the stimulation of neolymphogenesis and the formation of new lymph nodes. 3. The study provides the basis for further research into postnatal induced lymph nodes in cancer patients.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>неолимфогенез</kwd><kwd>лимфатические узлы</kwd><kwd>рак молочной железы</kwd><kwd>иммуногистохимия</kwd><kwd>CD3</kwd><kwd>CD20</kwd><kwd>CD68</kwd></kwd-group><kwd-group xml:lang="en"><kwd>neolymphogenesis</kwd><kwd>lymph nodes</kwd><kwd>breast cancer</kwd><kwd>immunohistochemistry</kwd><kwd>CD3</kwd><kwd>CD20</kwd><kwd>CD68</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Ганцев Ш.Х., Галеев М.Г., Ганцев К.Ш., Кзыргалин Ш.Р., Турсуметов Д.С., Рустамханов Р.А. и др. Лимфатический узел и его микроокружение при раке молочной железы. Москва: МИА; 2019. 280 с.</mixed-citation><mixed-citation xml:lang="en">Gantsev Sh.Kh., Galeev M.G., Gantsev K.Sh., Kzyrgalin Sh.R., Tursumetov D.S., Rustamkhanov R.A., et. al. Lymph node and its microenvironment in breast cancer. Moscow: MIA; 280 p. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Бородин Ю.И., Горчакова О.В., Горчаков В.Н. Периферические лимфоидные структуры: образование и функция. Морфология. 2016;(4):90–6.</mixed-citation><mixed-citation xml:lang="en">Borodin Yu.I., Gorchakova O.V., Gorchakov V.N. Peripheral lymphoid structures: formation and function. Morphology. 2016;(4):90–6 (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Corsiero E., Delvecchio F.R., Bombardieri M., Pitzalis C. B cells in the formation of tertiary lymphoid organs in autoimmunity, transplantation and tumorigenesis. Curr Opin Immunol. 2019;57:46–52. DOI: 10.1016/j.coi.2019.01.004</mixed-citation><mixed-citation xml:lang="en">Corsiero E., Delvecchio F.R., Bombardieri M., Pitzalis C. B cells in the formation of tertiary lymphoid organs in autoimmunity, transplantation and tumorigenesis. Curr Opin Immunol. 2019;57:46–52. DOI: 10.1016/j.coi.2019.01.004</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Ганцев Ш.Х., Рустамханов Р.А., Ганцев К.Ш., Кзыргалин Ш.Р. Третичные лимфоидные структуры (лимфоидный неогенез). Иммунология. 2019;40(2):58–63. DOI: 10.34411/0306-4953-301913008</mixed-citation><mixed-citation xml:lang="en">Gantsev Sh.Kh., Rustamkhanov R.A., Gantsev K.Sh., Kzyrgalin Sh.R. Tertiary lymphoid structures (lymphoid neogenesis). Immunologiya. 2019;40(2):58–63 (In Russ.). DOI: 10.34411/0306-4953-3019-13008</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Gantsev S.K., Umezawa K., Islamgulov D.V., Khusnutdinova E.K., Ishmuratova R.S., Frolova V.Y., et al. The role of inflammatory chemokines in lymphoid neoorganogenesis in breast cancer. Biomed Pharmacother. 2013;67(5):363–6. DOI: 10.1016/j.biopha.2013.03.017</mixed-citation><mixed-citation xml:lang="en">Gantsev S.K., Umezawa K., Islamgulov D.V., Khusnutdinova E.K., Ishmuratova R.S., Frolova V.Y., et al. The role of inflammatory chemokines in lymphoid neoorganogenesis in breast cancer. Biomed Pharmacother. 2013;67(5):363–6. DOI: 10.1016/j.biopha.2013.03.017</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Ганцев Ш.Х., Пухов А.Г., Хуснутдинова Э.К., Галеев М.Г., Ганцев К.Ш., Ишмуратова Р.Щ. и др. Неолимфогенез и профиль экспрессии хемокинов при раке молочной железы. Креативная хирургия и онкология. 2012;(1):4–9. DOI: 10.24060/2076-3093-2012-0-1-4-9</mixed-citation><mixed-citation xml:lang="en">Gantsev Sh.Kh., Pukhov A.G., Khusnutdinova E.K., Galeyev M.G., Gantsev K.Sh., Ishmuratova R.Sh., et al. Neolymphogenesis and chemokines’expression profile during breast cancer. Cteative surgery and oncology. 2012;(1):4–9 (In Russ.). DOI: 10.24060/2076-30932012-0-1-4-9</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Joyce J.A., Fearon D.T. T cell exclusion, immune privilege, and the tumor microenvironment. Science. 2015;(348):74–80. DOI: 10.1126/science.aaa6204</mixed-citation><mixed-citation xml:lang="en">Joyce J.A., Fearon D.T. T cell exclusion, immune privilege, and the tumor microenvironment. Science. 2015;(348):74–80. DOI: 10.1126/science.aaa6204</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Goc J., Germain C., Vo-Bourgais T.K.D., Lupo A., Klein C., Knockaert S., et al. Dendritic cells in tumor-associated tertiary lymphoid structures signal a Th1 cytotoxic immune contexture and license the positive prognostic value of infiltrating CD8+ T cells. Cancer Res. 2014;74(3):705–15. DOI: 10.1158/0008-5472. CAN-13-1342</mixed-citation><mixed-citation xml:lang="en">Goc J., Germain C., Vo-Bourgais T.K.D., Lupo A., Klein C., Knockaert S., et al. Dendritic cells in tumor-associated tertiary lymphoid structures signal a Th1 cytotoxic immune contexture and license the positive prognostic value of infiltrating CD8+ T cells. Cancer Res. 2014;74(3):705–15. DOI: 10.1158/0008-5472. CAN-13-1342</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Bento D.C., Jones E., Junaid S., Tull J., Williams G.T., Godkin A., et al. High endothelial venules are rare in colorectal cancers but accumulate in extra-tumoral areas with disease progression. Oncoimmunology. 2015;4(3):e974374. DOI: 10.4161/2162402X.2014.974374</mixed-citation><mixed-citation xml:lang="en">Bento D.C., Jones E., Junaid S., Tull J., Williams G.T., Godkin A., et al. High endothelial venules are rare in colorectal cancers but accumulate in extra-tumoral areas with disease progression. Oncoimmunology. 2015;4(3):e974374. DOI: 10.4161/2162402X.2014.974374</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Di Caro G., Bergomas F., Grizzi F., Doni A., Bianchi P., Malesci A., et al. Occurrence of tertiary lymphoid tissue is associated with T-cell infi ltration and predicts better prognosis in early-stage colorectal cancers. Clin Cancer Res. 2014;20(8):2147–58. DOI: 10.1158/1078-0432.CCR13-2590</mixed-citation><mixed-citation xml:lang="en">Di Caro G., Bergomas F., Grizzi F., Doni A., Bianchi P., Malesci A., et al. Occurrence of tertiary lymphoid tissue is associated with T-cell infi ltration and predicts better prognosis in early-stage colorectal cancers. Clin Cancer Res. 2014;20(8):2147–58. DOI: 10.1158/1078-0432. CCR-13-2590</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Figenschau S.L., Fismen S., Fenton K.A., Fenton C., Mortensen E.S. Tertiary lymphoid structures are associated with higher tumor grade in primary operable breast cancer patients. BMC Cancer. 2015;15:101. DOI: 10.1186/ s12885-015-1116-1</mixed-citation><mixed-citation xml:lang="en">Figenschau S.L., Fismen S., Fenton K.A., Fenton C., Mortensen E.S. Tertiary lymphoid structures are associated with higher tumor grade in primary operable breast cancer patients. BMC Cancer. 2015;15:101. DOI: 10.1186/ s12885-015-1116-1</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Song I.H., Heo S.-H., Bang W.S., Park H.S., Park I.A., Kim Y.A., et al. Predictive value of tertiary lymphoid structures assessed by high endothelial venule counts in the neoadjuvant setting of triple-negative breast cancer. Cancer Res Treat. 2017;49(2):399–407. DOI: 10.143/crt.2016.215</mixed-citation><mixed-citation xml:lang="en">Song I.H., Heo S.-H., Bang W.S., Park H.S., Park I.A., Kim Y.A., et al. Predictive value of tertiary lymphoid structures assessed by high endothelial venule counts in the neoadjuvant setting of triple-negative breast cancer. Cancer Res Treat. 2017;49(2):399–407. DOI: 10.4143/crt.2016.215</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">García-Hernández M.L., Uribe-Uribe N.O., Espinosa-González R., Kast W.M., Khader S.A., Rangel-Moreno J. A unique cellular and molecular microenvironment is present in tertiary lymphoid organs of patients with spontaneous prostate cancer regression. Front Immunol. 2017;8:563. DOI: 10.3389/fi mmu.2017.00563</mixed-citation><mixed-citation xml:lang="en">García-Hernández M.L., Uribe-Uribe N.O., Espinosa-González R., Kast W.M., Khader S.A., Rangel-Moreno J. A unique cellular and molecular microenvironment is present in tertiary lymphoid organs of patients with spontaneous prostate cancer regression. Front Immunol. 2017;8:563. DOI: 10.3389/fi mmu.2017.00563</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Kroeger D.R., Milne K., Nelson B.H. Tumor-infiltrating plasma cells are associated with tertiary lymphoid structures, cytolytic T-cell responses, and superior prognosis in ovarian cancer. Clin Cancer Res. 2016;22(12):3005–15. DOI: 10.1158/1078-0432.CCR-15-2762</mixed-citation><mixed-citation xml:lang="en">Kroeger D.R., Milne K., Nelson B.H. Tumor-infiltrating plasma cells are associated with tertiary lymphoid structures, cytolytic T-cell responses, and superior prognosis in ovarian cancer. Clin Cancer Res. 2016;22(12):3005–15. DOI: 10.1158/1078-0432.CCR-15-2762</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Hiraoka N., Ino Y., Yamazaki-Itoh R., Kanai Y., Kosuge T., Shimada K. Intratumoral tertiary lymphoid organ is a favourable prognosticator in patients with pancreatic cancer. Br J Cancer. 2015;112(11):1782–90. DOI: 10.1038/bjc.2015.145</mixed-citation><mixed-citation xml:lang="en">Hiraoka N., Ino Y., Yamazaki-Itoh R., Kanai Y., Kosuge T., Shimada K. Intratumoral tertiary lymphoid organ is a favourable prognosticator in patients with pancreatic cancer. Br J Cancer. 2015;112(11):1782–90. DOI: 10.1038/bjc.2015.145</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Finkin S., Yuan D., Stein I., Taniguchi K., Weber A., Unger K., et al. Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma. Nat Immunol. 2015;16(12):1235–44. DOI: 10.1038/ ni.3290</mixed-citation><mixed-citation xml:lang="en">Finkin S., Yuan D., Stein I., Taniguchi K., Weber A., Unger K., et al. Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma. Nat Immunol. 2015;16(12):1235–44. DOI: 10.1038/ ni.3290</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Sakai Y., Hoshino H., Kitazawa R., Kobayashi M. High endothelial venule-like vessels and lymphocyte recruitment in testicular seminoma. Andrology. 2014;2(2):282–9. DOI: 10.1111/j.2047-2927.2014.00192.x</mixed-citation><mixed-citation xml:lang="en">Sakai Y., Hoshino H., Kitazawa R., Kobayashi M. High endothelial venule-like vessels and lymphocyte recruitment in testicular seminoma. Andrology. 2014;2(2):282–9. DOI: 10.1111/j.20472927.2014.00192.x</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Giraldo N.A., Becht E., Pagès F., Skliris G., Verkarre V., Vano Y., et al. Orchestration and prognostic signifi cance of immune checkpoints in the microenvironment of primary and metastatic renal cell cancer. Clin Cancer Res. 2015;21(13):3031–40. DOI: 10.1158/1078-0432.CCR-14-2926</mixed-citation><mixed-citation xml:lang="en">Giraldo N.A., Becht E., Pagès F., Skliris G., Verkarre V., Vano Y., et al. Orchestration and prognostic signifi cance of immune checkpoints in the microenvironment of primary and metastatic renal cell cancer. Clin Cancer Res. 2015;21(13):3031–40. DOI: 10.1158/1078-0432.CCR-14-2926</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Low S., Sakai Y., Hoshino H., Hirokawa M., Kawashima H., Higuchi K., et al. High endothelial venule-like vessels and lymphocyte recruitment in diffuse sclerosing variant of papillary thyroid carcinoma. Pathology. 2016;48(7):666–74. DOI: 10.1016/j.pathol.2016.08.002</mixed-citation><mixed-citation xml:lang="en">Low S., Sakai Y., Hoshino H., Hirokawa M., Kawashima H., Higuchi K., et al. High endothelial venule-like vessels and lymphocyte recruitment in diffuse sclerosing variant of papillary thyroid carcinoma. Pathology. 2016;48(7):666–74. DOI: 10.1016/j.pathol.2016.08.002</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Ганцев Ш.Х. Новое к теории метастазирования рака и подходам к его лечению. Креативная хирургия и онкология. 2010;(4):5–11.</mixed-citation><mixed-citation xml:lang="en">Gantsev Sh.Kh. New in metastasis processing theory and in cancer treatment approachs. Creative surgery and oncology. 2012;(4):5–11 (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Dieu-Nosjean M.C., Giraldo N.A., Kaplon H., Germain C., Fridman W.H., Sautès-Fridman C. Tertiary lymphoid structures, drivers of the anti-tumor responses in human cancers. Immunol Rev. 2016;271(1):260–75. DOI: 10.1111/imr.12405</mixed-citation><mixed-citation xml:lang="en">Dieu-Nosjean M.C., Giraldo N.A., Kaplon H., Germain C., Fridman W.H., Sautès-Fridman C. Tertiary lymphoid structures, drivers of the anti-tumor responses in human cancers. Immunol Rev. 2016;271(1):260–75. DOI: 10.1111/imr.12405</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>
