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Иммунная гетерогенность рака молочной железы I стадии: биологическое, популяционное и прогностическое значение (опыт международного сотрудничества)
Иммунная гетерогенность рака молочной железы I стадии: биологическое, популяционное и прогностическое значение (опыт международного сотрудничества)
Колядина И.В., Поддубная И.В., van de Velde С.J.H. и др. Иммунная гетерогенность рака молочной железы I стадии: биологическое, популяционное и прогностическое значение (опыт международного сотрудничества). Современная онкология. 2015; 1: 30–38.
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Аннотация
Цель: изучить биологическое, популяционное и прогностическое значение иммунной гетерогенности опухолей при раке молочной железы (РМЖ) I стадии в двух независимых популяциях (российской и голландской).
Материалы и методы: изучены клинические, морфологические характеристики и течение заболевания у 518 больных РМЖ I стадии, которые получили лечение в ФГБНУ РОНЦ им. Н.Н.Блохина, клинике ГБОУ ДПО РМАПО (n=315) и Лейденском университетском медицинском центре – LUMC, Leiden University Medical Center (n=203) с 1985 по 2010 г. Парафиновые блоки опухолей пациенток были исследованы в LUMC; морфологические характеристики включали степень анаплазии, гистологический тип (определены на цельном опухолевом слайде) и опухолевые маркеры (ER, PR, HER2, Ki67, HC10, HCA2, HLA-E, HLA-G, Foxp3), экспрессия которых была исследована при иммуногистохимическом исследовании в микрочиповых образцах опухолей. Была изучена экспрессия иммунных маркеров у российских и голландских женщин, оценена иммунная гетерогенность РМЖ I стадии, также выделено 3 вида иммуногенности опухоли (высокая, умеренная и низкая). Была оценена популяционная и прогностическая роль иммуногенности для дальнейшего прогноза пациенток с РМЖ I стадии (в общей группе, подгруппах с/без адъювантной системной терапии). Статистический анализ выполнен с помощью международной статистической программы SPSS 20.0; различия считались достоверными при p<0,05.
Результаты исследования: иммунные характеристики опухолей при РМЖ I стадии имеют важные популяционные различия: опухоли российских больных высоко экспрессируют классические молекулы HLA I класса (HC10+ в 91%, HCA2+ в 48%, совместная экспрессия HC10+НСА2+ в 48% случаев), но и высоко экспрессируют неклассические маркеры HLA I класса (HLA-E+ в 99%, HLA-G+ в 26%). Кроме того, опухоли российских пациенток имеют высокую инфильтрацию Foxp3(+)-регуляторными клетками (в 73% случаев), что приводит к супрессии противоопухолевого ответа. В результате карциномы российских женщин являются высокоиммуногенными лишь в 14% случаев. Опухоли голландских пациенток умеренно презентируют классические молекулы HLA I класса (HC10+ в 74% случаев, HCA2+ в 41%, совместная экспрессия HC10+HCA2+ отмечена в 38% случаев), умеренно экспрессируют неклассические маркеры (HLA-E+ в 48%, HLA-G+ в 47%) и инфильтрированы Foxp3(+)-Т-регуляторными клетками лишь в 43%; высокая иммуногенность опухолей отмечена в 31% случаев, что может объяснять высокие показатели выживаемости при РМЖ I стадии у голландских женщин без адъювантной системной терапии. Иммуногенность опухоли – самостоятельный важный прогностический фактор для обеих популяций; отмечен высокий риск рецидива болезни и смерти от прогрессирования у больных с низкой иммуногенностью опухоли в общей группе пациенток и подгруппе женщин без адъювантной системной терапии. Применение адъювантной системной терапии может компенсировать негативное влияние низкой иммуногенности опухоли и существенно улучшить прогноз при РМЖ I стадии.
Ключевые слова: рак молочной железы I стадии, иммунобиология рака молочной железы, гены гистосовместимости HLA I класса, опухолевая инфильтрация Foxp3(+)-регуляторными клетками, иммуногенность рака молочной железы.
Materials and methods: we studied the clinical, morphological characteristics and disease course in 518 patients with stage I BC, who received treatment in N.N.Blokhin Russian Cancer Research Center, in the Hospital of Russian Medical Academy for Postgraduate Education of the Ministry of Health of the Russian Federation (n=315) and in Leiden University Medical Center – LUMC (n=203) between 1985 and 2010 years. Tumor tissue paraffin blocks had been examined at the LUMC; morphological characteristics were included the degree of anaplasia, histological type (solid tumor slide) and tumor markers (ER, PR, HER2, Ki67, HC10, HCA2, HLA-E, HLA-G, Foxp3), whose expression was validated by immunohistochemistry on tumor tissue microarrays. The expression of immune markers, the immunological heterogeneity of stage I BC were studied in Russian and Dutch women, and we also indicated 3 types of tumor immunogenicity (high, moderate, low). We studied population and prognostic role of immunogenicity as a further prediction in patients with stage I BC (in the general group, subgroups of patients treating with/without adjuvant systemic therapy). Statistical analysis was performed using international statistical program SPSS 20.0; differences were considered statistically significant when p<0,05.
Results: tumor immune characteristics in patients with stage I BC have important population-based differences: BC highly express molecules of HLA class I (HC10+ in 91%, HCA2+ in 48%, combined expression of the HC10+ nsa2+ in 48% of cases), and also highly express non-classical markers HLA class I (HLA-E+ in 99%, HLA-G+ in 26%) in russian women. The Russian women breast cancer is highly tumor-infiltrating Foxp3(+) regulatory T-cell (in 73% of cases), associated with the suppression of antitumor response. As a result, Russian women breast cancer is highly immunological only in 14% of the cases. Breast cancer in women in the Netherlands moderately presents the molecules of HLA class I (HC10+ in 74% of cases, HCA2+ in 41%, the combined expression of the HC10+HCA2+ in 38% of cases), moderately expresses non-classical markers (HLA-E+ in 48%, HLA-G+ in 47%) and the tumor-infiltrating Foxp3(+) regulatory T-cell is observed only in 43%; the high immunogenicity of the tumor is indicated in 31% of cases, which can explain the high survival rate in Dutch women suffering from stage I BC without using adjuvant systemic therapy. Immunogenicity of the tumor is the important prognostic factor for both populations; we have noted the higher risk of recurrence, disease progression and death in patients with low tumor immunogenicity in general group and subgroup of women with BC without using adjuvant systemic therapy. The use of adjuvant systemic therapy can help to neutralize the negative impact of low tumor immunogenicity and to significantly improve the prognosis in case of stage I BC.
Key words: stage I breast cancer, breast cancer immunobiology, HLA class I histocompatibility genes, tumor-infiltrating Foxp3(+) regulatory T-cell, immunogenicity of breast cancer.
Материалы и методы: изучены клинические, морфологические характеристики и течение заболевания у 518 больных РМЖ I стадии, которые получили лечение в ФГБНУ РОНЦ им. Н.Н.Блохина, клинике ГБОУ ДПО РМАПО (n=315) и Лейденском университетском медицинском центре – LUMC, Leiden University Medical Center (n=203) с 1985 по 2010 г. Парафиновые блоки опухолей пациенток были исследованы в LUMC; морфологические характеристики включали степень анаплазии, гистологический тип (определены на цельном опухолевом слайде) и опухолевые маркеры (ER, PR, HER2, Ki67, HC10, HCA2, HLA-E, HLA-G, Foxp3), экспрессия которых была исследована при иммуногистохимическом исследовании в микрочиповых образцах опухолей. Была изучена экспрессия иммунных маркеров у российских и голландских женщин, оценена иммунная гетерогенность РМЖ I стадии, также выделено 3 вида иммуногенности опухоли (высокая, умеренная и низкая). Была оценена популяционная и прогностическая роль иммуногенности для дальнейшего прогноза пациенток с РМЖ I стадии (в общей группе, подгруппах с/без адъювантной системной терапии). Статистический анализ выполнен с помощью международной статистической программы SPSS 20.0; различия считались достоверными при p<0,05.
Результаты исследования: иммунные характеристики опухолей при РМЖ I стадии имеют важные популяционные различия: опухоли российских больных высоко экспрессируют классические молекулы HLA I класса (HC10+ в 91%, HCA2+ в 48%, совместная экспрессия HC10+НСА2+ в 48% случаев), но и высоко экспрессируют неклассические маркеры HLA I класса (HLA-E+ в 99%, HLA-G+ в 26%). Кроме того, опухоли российских пациенток имеют высокую инфильтрацию Foxp3(+)-регуляторными клетками (в 73% случаев), что приводит к супрессии противоопухолевого ответа. В результате карциномы российских женщин являются высокоиммуногенными лишь в 14% случаев. Опухоли голландских пациенток умеренно презентируют классические молекулы HLA I класса (HC10+ в 74% случаев, HCA2+ в 41%, совместная экспрессия HC10+HCA2+ отмечена в 38% случаев), умеренно экспрессируют неклассические маркеры (HLA-E+ в 48%, HLA-G+ в 47%) и инфильтрированы Foxp3(+)-Т-регуляторными клетками лишь в 43%; высокая иммуногенность опухолей отмечена в 31% случаев, что может объяснять высокие показатели выживаемости при РМЖ I стадии у голландских женщин без адъювантной системной терапии. Иммуногенность опухоли – самостоятельный важный прогностический фактор для обеих популяций; отмечен высокий риск рецидива болезни и смерти от прогрессирования у больных с низкой иммуногенностью опухоли в общей группе пациенток и подгруппе женщин без адъювантной системной терапии. Применение адъювантной системной терапии может компенсировать негативное влияние низкой иммуногенности опухоли и существенно улучшить прогноз при РМЖ I стадии.
Ключевые слова: рак молочной железы I стадии, иммунобиология рака молочной железы, гены гистосовместимости HLA I класса, опухолевая инфильтрация Foxp3(+)-регуляторными клетками, иммуногенность рака молочной железы.
________________________________________________
Materials and methods: we studied the clinical, morphological characteristics and disease course in 518 patients with stage I BC, who received treatment in N.N.Blokhin Russian Cancer Research Center, in the Hospital of Russian Medical Academy for Postgraduate Education of the Ministry of Health of the Russian Federation (n=315) and in Leiden University Medical Center – LUMC (n=203) between 1985 and 2010 years. Tumor tissue paraffin blocks had been examined at the LUMC; morphological characteristics were included the degree of anaplasia, histological type (solid tumor slide) and tumor markers (ER, PR, HER2, Ki67, HC10, HCA2, HLA-E, HLA-G, Foxp3), whose expression was validated by immunohistochemistry on tumor tissue microarrays. The expression of immune markers, the immunological heterogeneity of stage I BC were studied in Russian and Dutch women, and we also indicated 3 types of tumor immunogenicity (high, moderate, low). We studied population and prognostic role of immunogenicity as a further prediction in patients with stage I BC (in the general group, subgroups of patients treating with/without adjuvant systemic therapy). Statistical analysis was performed using international statistical program SPSS 20.0; differences were considered statistically significant when p<0,05.
Results: tumor immune characteristics in patients with stage I BC have important population-based differences: BC highly express molecules of HLA class I (HC10+ in 91%, HCA2+ in 48%, combined expression of the HC10+ nsa2+ in 48% of cases), and also highly express non-classical markers HLA class I (HLA-E+ in 99%, HLA-G+ in 26%) in russian women. The Russian women breast cancer is highly tumor-infiltrating Foxp3(+) regulatory T-cell (in 73% of cases), associated with the suppression of antitumor response. As a result, Russian women breast cancer is highly immunological only in 14% of the cases. Breast cancer in women in the Netherlands moderately presents the molecules of HLA class I (HC10+ in 74% of cases, HCA2+ in 41%, the combined expression of the HC10+HCA2+ in 38% of cases), moderately expresses non-classical markers (HLA-E+ in 48%, HLA-G+ in 47%) and the tumor-infiltrating Foxp3(+) regulatory T-cell is observed only in 43%; the high immunogenicity of the tumor is indicated in 31% of cases, which can explain the high survival rate in Dutch women suffering from stage I BC without using adjuvant systemic therapy. Immunogenicity of the tumor is the important prognostic factor for both populations; we have noted the higher risk of recurrence, disease progression and death in patients with low tumor immunogenicity in general group and subgroup of women with BC without using adjuvant systemic therapy. The use of adjuvant systemic therapy can help to neutralize the negative impact of low tumor immunogenicity and to significantly improve the prognosis in case of stage I BC.
Key words: stage I breast cancer, breast cancer immunobiology, HLA class I histocompatibility genes, tumor-infiltrating Foxp3(+) regulatory T-cell, immunogenicity of breast cancer.
Полный текст
Список литературы
1. Nicolini A, Carpi A. Immune manipulation of advanced breast cancer: an interpretative model of the relationship between immune system and tumor cell biology. Med Res Rev 2009; 29: 436–71.
2. De Kruijf EM, Sajet A, van Nes JG et al. HLA-E and HLA-G expression in classical HLA class I-negative tumors is of prognostic value for clinical outcome of early breast cancer patients. J Immunol 2010; 185: 7452–9.
3. Engels CC, Charehbili A, Van de Velde CJ et al. The prognostic and predictive value of Tregs and tumor immune subtypes in postmenopausal, hormone receptor-positive breast cancer patients treated with adjuvant endocrine therapy: a Dutch TEAM study analysis. Breast Cancer Res Treat 2015; 149 (3): 587–96.
4. García-Martínez E, Luengo Gil G, Chaves Benito A Tumor-infiltrating immune cell profiles and their change after neoadjuvant chemotherapy predict response and prognosis of breast cancer. Breast Cancer Res 2014; 16 (6): 488.
5. Finn OJ. Cancer immunology. N Engl J Med 2008; 358: 2704–15.
6. Kaneko K, Ishigami S, Kijima Y. Clinical implication of HLA class I expression in breast cancer. BMC Cancer 2011; 11: 454.
7. Cabrera T, Angustias Fernandez M, Sierra A et al. High frequency of altered HLA class I phenotypes in invasive breast carcinomas. Hum Immunol 1996; 50: 127–34.
8. Klein J, Sato A. The HLA system. First of two parts. N Engl J Med 2000; 343: 702–9.
9. Powell AG, Horgan PG, Edwards J. The bodies fight against cancer: is human leucocyte antigen (HLA) class 1 the key? J Cancer Res Clin Oncol 2012; 138: 723–8.
10. Shenouda G, Thomson DM. Blocking of the response by human T-lymphocytes to extracts of autologous cancer by monoclonal antibody to Class-I major histocompatibility complex gene products in the leukocyte adherence inhibition assay. Cancer Res 1984; 44 (7): 2762–8.
11. Curigliano G, Criscitiello C, Gelao L. Molecular pathways: human leukocyte antigen G (HLA-G). Clin Cancer Res 2013; 19 (20): 5564–71.
12. Dong DD, Yie SM, Li K et al. Importance of HLA-G expression and tumor infiltrating lymphocytes in molecular subtypes of breast cancer. Hum Immunol 2012; 73: 998–1004.
13. Ramos CS, Gonçalves AS, Marinho LC. Analysis of HLA-G gene polymorphism and protein expression in invasive breast ductal carcinoma. Hum Immunol 2014; 75 (7): 667–72.
14. Da Silva GB, Silva TG, Duarte RA. Expression of the Classical and Nonclassical HLA Molecules in Breast Cancer. Int J Breast Cancer 2013; 2013: 250–435.
15. Jeong S, Park S, Park BW. Human leukocyte antigen-G (HLA-G) polymorphism and expression in breast cancer patients. PLoS One 2014; 9 (5): e98284.
16. Mao Y, Qu Q, Zhang Y. The value of tumor infiltrating lymphocytes (TILs) for predicting response to neoadjuvant chemotherapy inbreast cancer: a systematic review and meta-analysis. PLoS One 2014; 9 (12): e115103.
17. Chan MS, Chen SF, Felizola SJ Correlation of tumor-infiltrative lymphocyte subtypes alteration with neoangiogenesis before and after neoadjuvant chemotherapy treatment in breast cancer patients. Int J Biol Markers 2014; 29 (3): e193–203.
18. Kim ST, Jeong H, Woo OH. Tumor-infiltrating lymphocytes, tumor characteristics, and recurrence in patients with early breast cancer. Am J Clin Oncol 2013; 36 (3): 224–31.
19. Miyashita M, Sasano H, Tamaki K. Tumor-infiltrating CD8+ and FOXP3+ lymphocytes in triple-negative breast cancer: its correlation with pathological complete response to neoadjuvant chemotherapy. Breast Cancer Res Treat 2014; 148 (3): 525–34.
20. Liu S, Foulkes WD, Leung S. Prognostic significance of FOXP3+ tumor-infiltrating lymphocytes in breast cancer depends on estrogen receptor and human epidermal growth factor receptor-2 expression status and concurrent cytotoxic T-cell infiltration. Breast Cancer Res 2014; 16 (5): 432.
21. De Kruijf EM, Engels CC, Van de Water W. Tumor immune subtypes distinguish tumor subclasses with clinical implications in breast cancer patients. Breast Cancer Res Treat 2013; 142 (2): 355–64.
2. De Kruijf EM, Sajet A, van Nes JG et al. HLA-E and HLA-G expression in classical HLA class I-negative tumors is of prognostic value for clinical outcome of early breast cancer patients. J Immunol 2010; 185: 7452–9.
3. Engels CC, Charehbili A, Van de Velde CJ et al. The prognostic and predictive value of Tregs and tumor immune subtypes in postmenopausal, hormone receptor-positive breast cancer patients treated with adjuvant endocrine therapy: a Dutch TEAM study analysis. Breast Cancer Res Treat 2015; 149 (3): 587–96.
4. García-Martínez E, Luengo Gil G, Chaves Benito A Tumor-infiltrating immune cell profiles and their change after neoadjuvant chemotherapy predict response and prognosis of breast cancer. Breast Cancer Res 2014; 16 (6): 488.
5. Finn OJ. Cancer immunology. N Engl J Med 2008; 358: 2704–15.
6. Kaneko K, Ishigami S, Kijima Y. Clinical implication of HLA class I expression in breast cancer. BMC Cancer 2011; 11: 454.
7. Cabrera T, Angustias Fernandez M, Sierra A et al. High frequency of altered HLA class I phenotypes in invasive breast carcinomas. Hum Immunol 1996; 50: 127–34.
8. Klein J, Sato A. The HLA system. First of two parts. N Engl J Med 2000; 343: 702–9.
9. Powell AG, Horgan PG, Edwards J. The bodies fight against cancer: is human leucocyte antigen (HLA) class 1 the key? J Cancer Res Clin Oncol 2012; 138: 723–8.
10. Shenouda G, Thomson DM. Blocking of the response by human T-lymphocytes to extracts of autologous cancer by monoclonal antibody to Class-I major histocompatibility complex gene products in the leukocyte adherence inhibition assay. Cancer Res 1984; 44 (7): 2762–8.
11. Curigliano G, Criscitiello C, Gelao L. Molecular pathways: human leukocyte antigen G (HLA-G). Clin Cancer Res 2013; 19 (20): 5564–71.
12. Dong DD, Yie SM, Li K et al. Importance of HLA-G expression and tumor infiltrating lymphocytes in molecular subtypes of breast cancer. Hum Immunol 2012; 73: 998–1004.
13. Ramos CS, Gonçalves AS, Marinho LC. Analysis of HLA-G gene polymorphism and protein expression in invasive breast ductal carcinoma. Hum Immunol 2014; 75 (7): 667–72.
14. Da Silva GB, Silva TG, Duarte RA. Expression of the Classical and Nonclassical HLA Molecules in Breast Cancer. Int J Breast Cancer 2013; 2013: 250–435.
15. Jeong S, Park S, Park BW. Human leukocyte antigen-G (HLA-G) polymorphism and expression in breast cancer patients. PLoS One 2014; 9 (5): e98284.
16. Mao Y, Qu Q, Zhang Y. The value of tumor infiltrating lymphocytes (TILs) for predicting response to neoadjuvant chemotherapy inbreast cancer: a systematic review and meta-analysis. PLoS One 2014; 9 (12): e115103.
17. Chan MS, Chen SF, Felizola SJ Correlation of tumor-infiltrative lymphocyte subtypes alteration with neoangiogenesis before and after neoadjuvant chemotherapy treatment in breast cancer patients. Int J Biol Markers 2014; 29 (3): e193–203.
18. Kim ST, Jeong H, Woo OH. Tumor-infiltrating lymphocytes, tumor characteristics, and recurrence in patients with early breast cancer. Am J Clin Oncol 2013; 36 (3): 224–31.
19. Miyashita M, Sasano H, Tamaki K. Tumor-infiltrating CD8+ and FOXP3+ lymphocytes in triple-negative breast cancer: its correlation with pathological complete response to neoadjuvant chemotherapy. Breast Cancer Res Treat 2014; 148 (3): 525–34.
20. Liu S, Foulkes WD, Leung S. Prognostic significance of FOXP3+ tumor-infiltrating lymphocytes in breast cancer depends on estrogen receptor and human epidermal growth factor receptor-2 expression status and concurrent cytotoxic T-cell infiltration. Breast Cancer Res 2014; 16 (5): 432.
21. De Kruijf EM, Engels CC, Van de Water W. Tumor immune subtypes distinguish tumor subclasses with clinical implications in breast cancer patients. Breast Cancer Res Treat 2013; 142 (2): 355–64.
2. De Kruijf EM, Sajet A, van Nes JG et al. HLA-E and HLA-G expression in classical HLA class I-negative tumors is of prognostic value for clinical outcome of early breast cancer patients. J Immunol 2010; 185: 7452–9.
3. Engels CC, Charehbili A, Van de Velde CJ et al. The prognostic and predictive value of Tregs and tumor immune subtypes in postmenopausal, hormone receptor-positive breast cancer patients treated with adjuvant endocrine therapy: a Dutch TEAM study analysis. Breast Cancer Res Treat 2015; 149 (3): 587–96.
4. García-Martínez E, Luengo Gil G, Chaves Benito A Tumor-infiltrating immune cell profiles and their change after neoadjuvant chemotherapy predict response and prognosis of breast cancer. Breast Cancer Res 2014; 16 (6): 488.
5. Finn OJ. Cancer immunology. N Engl J Med 2008; 358: 2704–15.
6. Kaneko K, Ishigami S, Kijima Y. Clinical implication of HLA class I expression in breast cancer. BMC Cancer 2011; 11: 454.
7. Cabrera T, Angustias Fernandez M, Sierra A et al. High frequency of altered HLA class I phenotypes in invasive breast carcinomas. Hum Immunol 1996; 50: 127–34.
8. Klein J, Sato A. The HLA system. First of two parts. N Engl J Med 2000; 343: 702–9.
9. Powell AG, Horgan PG, Edwards J. The bodies fight against cancer: is human leucocyte antigen (HLA) class 1 the key? J Cancer Res Clin Oncol 2012; 138: 723–8.
10. Shenouda G, Thomson DM. Blocking of the response by human T-lymphocytes to extracts of autologous cancer by monoclonal antibody to Class-I major histocompatibility complex gene products in the leukocyte adherence inhibition assay. Cancer Res 1984; 44 (7): 2762–8.
11. Curigliano G, Criscitiello C, Gelao L. Molecular pathways: human leukocyte antigen G (HLA-G). Clin Cancer Res 2013; 19 (20): 5564–71.
12. Dong DD, Yie SM, Li K et al. Importance of HLA-G expression and tumor infiltrating lymphocytes in molecular subtypes of breast cancer. Hum Immunol 2012; 73: 998–1004.
13. Ramos CS, Gonçalves AS, Marinho LC. Analysis of HLA-G gene polymorphism and protein expression in invasive breast ductal carcinoma. Hum Immunol 2014; 75 (7): 667–72.
14. Da Silva GB, Silva TG, Duarte RA. Expression of the Classical and Nonclassical HLA Molecules in Breast Cancer. Int J Breast Cancer 2013; 2013: 250–435.
15. Jeong S, Park S, Park BW. Human leukocyte antigen-G (HLA-G) polymorphism and expression in breast cancer patients. PLoS One 2014; 9 (5): e98284.
16. Mao Y, Qu Q, Zhang Y. The value of tumor infiltrating lymphocytes (TILs) for predicting response to neoadjuvant chemotherapy inbreast cancer: a systematic review and meta-analysis. PLoS One 2014; 9 (12): e115103.
17. Chan MS, Chen SF, Felizola SJ Correlation of tumor-infiltrative lymphocyte subtypes alteration with neoangiogenesis before and after neoadjuvant chemotherapy treatment in breast cancer patients. Int J Biol Markers 2014; 29 (3): e193–203.
18. Kim ST, Jeong H, Woo OH. Tumor-infiltrating lymphocytes, tumor characteristics, and recurrence in patients with early breast cancer. Am J Clin Oncol 2013; 36 (3): 224–31.
19. Miyashita M, Sasano H, Tamaki K. Tumor-infiltrating CD8+ and FOXP3+ lymphocytes in triple-negative breast cancer: its correlation with pathological complete response to neoadjuvant chemotherapy. Breast Cancer Res Treat 2014; 148 (3): 525–34.
20. Liu S, Foulkes WD, Leung S. Prognostic significance of FOXP3+ tumor-infiltrating lymphocytes in breast cancer depends on estrogen receptor and human epidermal growth factor receptor-2 expression status and concurrent cytotoxic T-cell infiltration. Breast Cancer Res 2014; 16 (5): 432.
21. De Kruijf EM, Engels CC, Van de Water W. Tumor immune subtypes distinguish tumor subclasses with clinical implications in breast cancer patients. Breast Cancer Res Treat 2013; 142 (2): 355–64.
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2. De Kruijf EM, Sajet A, van Nes JG et al. HLA-E and HLA-G expression in classical HLA class I-negative tumors is of prognostic value for clinical outcome of early breast cancer patients. J Immunol 2010; 185: 7452–9.
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Авторы
И.В.Колядина*1, 2, И.В.Поддубная1, 2, С.J.H.van de Velde3, P.Kuppen3, Г.А.Франк1, Д.В.Комов2, А.И.Карселадзе2, E.Bastiaannet3, N.G.Dekker-Ensink3
1 ГБОУ ДПО Российская медицинская академия последипломного образования Минздрава России. 125993, Россия, Москва, ул. Баррикадная, д. 2/1;
2 ФГБНУ Российский онкологический научный центр им. Н.Н.Блохина. 115478, Россия, Москва, Каширское ш., д. 23;
3 Лейденский университетский медицинский центр (LUMC). Нидерланды, Лейден, Department of Surgery, K6-R P.O. Box 9600, 2300 RC
*irinakolyadina@yandex.ru
1 Russian Medical Academy for Postgraduate Education of the Ministry of Health of the Russian Federation. 125993 Russian Federation, Moscow, ul. Barrikadnaia, d. 2/1;
2 N.N.Blokhin Russian Cancer Research Center. 115478, Russian Federation, Moscow, Kashirskoe sh., d. 23;
3 Leiden University Medical Center (LUMC). Leiden, The Netherlands, Department of Surgery, K6-R P.O. Box 9600, 2300 RC
*irinakolyadina@yandex.ru
1 ГБОУ ДПО Российская медицинская академия последипломного образования Минздрава России. 125993, Россия, Москва, ул. Баррикадная, д. 2/1;
2 ФГБНУ Российский онкологический научный центр им. Н.Н.Блохина. 115478, Россия, Москва, Каширское ш., д. 23;
3 Лейденский университетский медицинский центр (LUMC). Нидерланды, Лейден, Department of Surgery, K6-R P.O. Box 9600, 2300 RC
*irinakolyadina@yandex.ru
________________________________________________
1 Russian Medical Academy for Postgraduate Education of the Ministry of Health of the Russian Federation. 125993 Russian Federation, Moscow, ul. Barrikadnaia, d. 2/1;
2 N.N.Blokhin Russian Cancer Research Center. 115478, Russian Federation, Moscow, Kashirskoe sh., d. 23;
3 Leiden University Medical Center (LUMC). Leiden, The Netherlands, Department of Surgery, K6-R P.O. Box 9600, 2300 RC
*irinakolyadina@yandex.ru
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