Ulyanovsk Medico-biological Journal

CLINICAL MEDICINE

Download article

DOI 10.34014/2227-1848-2023-3-95-108

EXPRESSION OF PROGRAMMED CELL DEATH PROTEIN 1 (PD-1) AND ITS LIGAND PD-L1 IN HIGH-GRADE SEROUS OVARIAN CANCER

V.N. Zhurman1, N.G. Plekhova2

1Primorsky Regional Oncological Dispensary, Vladivostok, Russia;

2 Pacific State Medical University, Ministry of Health of the Russian Federation, Vladivostok, Russia

 

Recently, the immunotherapeutic treatment of ovarian cancer is of much concern. This is due to the discovery of the signaling pathway of the PD-1/PD-L1 immune checkpoints, which are capable of controlling autoimmune response severity and duration.

The aim of the study is to determine the dependence of PD-1/PD-L1 expression on the proliferative activity of high-grade serous ovarian cancer cells.

Materials and Methods. The study was performed at Central Research Laboratory, Pacific State Medical University, Ministry of Health of the Russian Federation. The material was collected at Primorsky Regional Oncological Dispensary, 2016–2021. The pathological and anatomical samples were analyzed by immunohistochemistry using p53, Ki-67, PD-L1, and Anti-Hu CD279 (PD-1). The main group included 74 patients with high-grade serous ovarian cancer, the comparative group consisted of 26 patients with benign ovarian tumors.

Results. PD-1/PD-L1 expression was observed in tumor tissues in ovarian cancer. There was also an increase in the positive reaction to Ki-67 and p53 according to grading and staging of cancer.

Conclusion. Despite the claimed immunomodulatory function, high PD-1/PD-L1 levels are favorable prognostic indicators in ovarian cancer. The obtained data show that PD-1/PD-L1 molecules are biologically significant regulators of the immune response in high-grade serous ovarian cancer, which is an argument in favor of immune checkpoint inhibitors. Thus, PD-L1 in the immune cells infiltrating the tumor is a favorable prognostic factor. A statistically significant direct correlation between Ki-67 and PD-L1 proves a direct dependence of PD-L1 expression on proliferative activity of the ovarian tumor. A statistically significant inverse correlation between p53 and PD-1 shows the dependence of PD-1 expression on apoptotic changes in the ovarian tumor.

Key words: ovarian cancer, Ki-67, p53, PD-1/PD-L1.

 

Conflict of interest. The authors declare no conflict of interest.

Author contributions

Research concept and design: Zhurman V.N., Plekhova N.G.

Literature search: Zhurman V.N.

Data collection, analysis and interpretation: Zhurman V.N., Plekhova N.G.

Text writing and editing: Zhurman V.N., Plekhova N.G.

 

References

  1. Ishida Y., Agata Y., Shibahara K., Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992; 11 (11): 3887–3895. DOI: 10.1002/j.1460-2075.1992.tb05481.x.

  2. Zhu X., Jinghe L. The significance and therapeutic potential of PD-1 and its ligands in ovarian cancer: A systematic review. Gynecologic oncology. 2016; 142 (1): 184–189. DOI: 10.1016/j.ygyno.2016.04.002.

  3. Dong H., Zhu G., Tamada K., Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999; 5 (12): 1365–1369. DOI: 10.1038/70932.

  4. Kushlinskiy N.E., Gershteyn E.S., Goryacheva I.O. Rastvorimye formy retseptora kontrol'noy tochki immuniteta PD-1 i ego liganda PD-L1 v syvorotke krovi bol'nykh pochechno-kletochnym rakom: kliniko-morfologicheskie korrelyatsii [Soluble forms of the immune checkpoint receptor PD-1 and its ligand PD-L1 in blood serum of patients with renal cell carcinoma: Clinical and pathologic correlations]. Onkourologiya. 2019; 15 (1): 15–22 (in Russian).

  5. Nishimura H., Honjo T., Minato N. Facilitation of beta selection and modification of positive selection in the thymus of PD-1-deficient mice. J. Exp Med. 2000; 191 (5): 891–898. DOI: 10.1084/jem.191.5.891.

  6. Guo X., Wang J., Jin J., Chen H., Zhen Z., Jiang W., Lin T., Huang H., Xia Z., Sun X. High Serum Level of Soluble Programmed Death Ligand 1 is Associated With a Poor Prognosis in Hodgkin Lymphoma. Translational oncology. 2018; 11 (3): 779–785. DOI: https://doi.org/10.1016/j.tranon.2018.03.012.

  7. Francisco L.M., Salinas V.H., Brown K.E., Vanguri V.K., Freeman G.J., Kuchroo V.K., Sharpe A.H. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. The Journal of experimental medicine. 2009; 206 (13): 3015–3029. DOI: https://doi.org/10.1084/jem.20090847.

  8. Sayapina M.S. Immunoregulatory functions of PD-1/PD-L1 inhibitors and development of resistance to them. Malignant Tumors. 2017; 2: 94–99.

  9. Gadducci Angiolo, Maria Elena Guerrieri. Immune Checkpoint Inhibitors in Gynecological Cancers: Update of Literature and Perspectives of Clinical Research. Anticancer research. 2017; 37 (11): 5955–5965. DOI: 10.21873/anticanres.12042.

  10. Rosenwald A., Wright G., Leroy K., Yu X., Gaulard P., Gascoyne R.D., Chan W.C., Zhao T., Haioun C., Greiner T.C., Weisenburger D.D., Lynch J.C., Vose J., Armitage J.O., Smeland E.B., Kvaloy S., Holte H., Delabie J., Campo E., Montserrat E., Staudt L.M. Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. The Journal of experimental medicine. 2003; 198 (6): 851–862. DOI: https://doi.org/10.1084/jem.20031074.

  11. Maleki V.S., Garrigos C., Duran I. Biomarkers of response to PD-1/PD-L1 inhibition. Crit Rev Oncol Hematol. 2017; 116: 116–124. DOI: 10.1016/j.critrevonc.2017.06.001.

  12. Yuasa T., Masuda H., Yamamoto S., Numao N., Yonese J. Biomarkers to predict prognosis and response to checkpoint inhibitors. Int J Clin Oncol. 2017; 22 (4): 629–634. DOI: 10.1007/s10147-017-1122-1.

  13. Huang X., Zhang W., Zhang Z., Shi D., Wu F., Zhong B., Shao Z. Prognostic Value of Programmed Cell Death 1 Ligand-1 (PD-L1) or PD-1 Expression in Patients with Osteosarcoma: A Meta-Analysis. Journal of Cancer. 2018; 9 (14): 2525–2531. DOI: https://doi.org/10.7150/jca.25011.

  14. Kim K.S., Sekar R.R., Patil D., Dimarco M.A., Kissick H.T., Bilen M.A., Osunkoya A.O., Master V.A. Evaluation of programmed cell death protein 1 (PD-1) expression as a prognostic biomarker in patients with clear cell renal cell carcinoma. Oncoimmunology. 2018; 7 (4): e1413519. DOI: https://doi.org/

    10.1080/2162402X.2017.1413519.

  15. Sacher A.G., Leena G. Biomarkers for the Clinical Use of PD-1/PD-L1 Inhibitors in Non-Small-Cell Lung Cancer: A Review. JAMA oncology. 2016; 2 (9): 1217–1222. DOI: 10.1001/jamaoncol.2016.0639.

  16. Darb-Esfahani S., Kunze C.A., Kulbe H., Sehouli J., Wienert S., Lindner J., Budczies J., Bockmayr M., Dietel M., Denkert C., Braicu I., Jöhrens K. Prognostic impact of programmed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor-infiltrating lymphocytes in ovarian high grade serous carcinoma. Oncotarget. 2016; 7 (2): 1486–1499. DOI: https://doi.org/10.18632/oncotarget.6429.

  17. Drakes M.L., Mehrotra S., Aldulescu M., Potkul R.K., Liu Y., Grisoli A., Joyce C., O'Brien T.E., Stack M.S., Stiff P.J. Stratification of ovarian tumor pathology by expression of programmed cell death-1 (PD-1) and PD-ligand-1 (PD-L1) in ovarian cancer. Journal of ovarian research. 2018; 11 (1): 43. DOI: https://doi.org/10.1186/s13048-018-0414-z.

  18. Strickland K.C., Howitt B.E., Shukla S.A., Rodig S., Ritterhouse L.L., Liu J.F., Garber J.E., Chowdhury D., Wu C.J., D'Andrea A.D., Matulonis U.A., Konstantinopoulos P.A. Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer. Oncotarget. 2016; 7 (12): 13587–13598. DOI: https://doi.org/10.18632/oncotarget.7277.

  19. Wieser V., Gaugg I., Fleischer M., Shivalingaiah G., Wenzel S., Sprung S., Lax S.F., Zeimet A.G., Fiegl H., Marth C. BRCA1/2 and TP53 mutation status associates with PD-1 and PD-L1 expression in ovarian cancer. Oncotarget. 2018; 9 (25): 17501–17511. DOI: https://doi.org/10.18632/oncotarget.24770.

  20. Inayama Y., Hamanishi J., Matsumura N., Murakami R., Abiko K., Yamaguchi K., Baba T., Horie K., Konishi I., Mandai M. Antitumor Effect of Nivolumab on Subsequent Chemotherapy for Platinum-Resistant Ovarian Cancer. The oncologist. 2018; 23 (11): 1382–1384. DOI: https://doi.org/10.1634/theoncologist.2018-0167.

  21. Zhu X., Xu J., Cai H., Lang J. Carboplatin and programmed death-ligand 1 blockade synergistically produce a similar antitumor effect to carboplatin alone in murine ID8 ovarian cancer model. J Obstet Gynaecol Res. 2018; 44 (2): 303–311. DOI: 10.1111/jog.13521.

  22. Yudina A.S., Abizyaeva I.L., Yudin S.V., Zhernovoy M.V. Organizatsionnye problemy profilakticheskoy onkologii organov reproduktivnoy sistemy zhenshchin [Organizational problems of preventive oncology of female reproductive system]. Tikhookeanskiy meditsinskiy zhurnal. 2007; 4: 83–84 (in Russian).

  23. Mittendorf E.A., Philips A.V., Meric-Bernstam F., Qiao N., Wu Y., Harrington S., Su X., Wang Y., Gonzalez-Angulo A.M., Akcakanat A., Chawla A., Curran M., Hwu P., Sharma P., Litton J. K., Molldrem J.J., Alatrash G. PD-L1 expression in triple-negative breast cancer. Cancer immunology research. 2014; 2 (4): 361–370. DOI: https://doi.org/10.1158/2326-6066.CIR-13-0127.

  24. Wimberly H., Brown J.R., Schalper K., Haack H., Silver M.R., Nixon C., Bossuyt V., Pusztai L., Lannin D.R., Rimm D.L. PD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer. Cancer immunology research. 2015; 3 (4): 326–332. DOI: https://doi.org/10.1158/2326-6066.CIR-14-0133.

  25. Ding Y., Sun C., Li J., Hu L., Li M., Liu J., Pu L., Xiong S. The Prognostic Significance of Soluble Programmed Death Ligand 1 Expression in Cancers: A Systematic Review and Meta-analysis. Scandinavian journal of immunology. 2017; 86 (5): 361–367. DOI: https://doi.org/10.1111/sji.12596.

  26. Theodoraki M.N., Yerneni S.S., Hoffmann T.K., Gooding W.E., Whiteside T.L. Clinical Significance of PD-L1+ Exosomes in Plasma of Head and Neck Cancer Patients. Clin Cancer Res. 2018; 24 (4): 896–905. DOI: 10.1158/1078-0432.CCR-17-2664.

  27. Wei W., Xu B., Wang Y., Wu C., Jiang J., Wu C. Prognostic significance of circulating soluble programmed death ligand-1 in patients with solid tumors: A meta-analysis. Medicine (Baltimore). 2018; 97 (3): e9617. DOI: 10.1097/MD.0000000000009617.

 

Received November 01, 2022; accepted April 05, 2023.

 

Information about the authors

Zhurman Varvara Nikolaevna, Candidate of Sciences (Medicine), Oncologist, Primorsky Regional Oncology Dispensary. 690000, Russia, Vladivostok, Russkaya St., 63A; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: http://orcid.org/0000-0002-6927-3336

Plekhova Natal'ya Gennad'evna, Doctor of Sciences (Biology), Head of the Central Research Laboratory, Professor, Chair of Clinical Laboratory Diagnostics, General and Clinical Immunology, Pacific State Medical University, Ministry of Health of the Russian Federation. 690002, Vladivostok, Ostryakov Ave., 2; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: http://orcid.org/0000-0002-8701-7213

 

For citation

Zhurman V.N., Plekhova N.G. Ekspressiya retseptora k belku programmirovannoy gibeli kletok PD-1 i ego liganda PD-L1 pri seroznom rake yaichnikov high-grade [Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in high-grade serous ovarian cancer]. Ul'yanovskiy mediko-biologicheskiy zhurnal. 2023; 3: 95–108. DOI: 10.34014/2227-1848-2023-3-95-108 (in Russian).

 

Скачать статью

УДК 61-616-018

DOI 10.34014/2227-1848-2023-3-95-108

ЭКСПРЕССИЯ РЕЦЕПТОРА К БЕЛКУ ПРОГРАММИРОВАННОЙ ГИБЕЛИ КЛЕТОК PD-1 И ЕГО ЛИГАНДА PD-L1 ПРИ СЕРОЗНОМ РАКЕ ЯИЧНИКОВ HIGH-GRADE

В.Н. Журман1, Н.Г. Плехова2

1 ГБУЗ «Приморский краевой онкологический диспансер», г. Владивосток, Россия;

2 ФГБОУ ВО «Тихоокеанский государственный медицинский университет» Министерства здравоохранения Российской Федерации, г. Владивосток, Россия

 

В последнее время большой интерес вызывает иммунотерапевтическое лечение рака яичников. Это связано с открытием сигнального пути чекпойнтов (контрольных точек) иммунитета PD-1/PD-L1, способных осуществлять управление выраженностью и продолжительностью аутоиммунного ответа.

Цель. Определить зависимость уровня экспрессии рецептора PD-1 и его лиганда PD-L1 от степени пролиферативной активности клеток серозного рака яичников high-grade.

Материалы и методы. Исследование выполнено в ФГБОУ ВО «Тихоокеанский государственный медицинский университет» Минздрава России на базе Центральной научно-исследовательской лаборатории. Материал взят в ГБУЗ «Приморский краевой онкологический диспансер» в период с 2016 по 2021 г. Проведен анализ патологоанатомического материала методом иммуногистохимии с использованием антител p53, Ki-67, PD-L1, Anti-Hu CD279 (PD-1). В основную группу вошли 74 пациентки с серозным раком яичников high-grade, в сравнительную – 26 пациенток с доброкачественными опухолями яичников.

Результаты. Установлено наличие экспрессии рецептора PD-1 и лиганда PD-L1 в опухолевых тканях при раке яичников. Определено повышение позитивной реакции на Ki-67 и р53 в зависимости от степени дифференцировки и стадии опухолевого процесса.

Выводы. Несмотря на заявленную иммуномодулирующую функцию, высокие уровни PD-1 и PD-L1 являются индикаторами благоприятного прогноза при раке яичников. Полученные данные показывают, что молекулы PD-1 и PD-L1 являются биологически значимыми регуляторами иммунного ответа при серозном раке яичников high-grade, что служит аргументом в пользу оценки противоопухолевых лекарственных препаратов, ингибирующих иммунные контрольные точки. Вышесказанное позволяет утверждать, что продукция лиганда PD-L1 в клетках иммунной системы, которые инфильтрируют опухоль, рассматривается как благоприятный прогностический фактор. Статистически значимая прямая связь между Ki-67 и PD-L1 доказывает прямую зависимость экспрессии лиганда PD-L1 от степени пролиферативной активности опухоли яичников. Статистически значимая обратная связь между p53 и PD-1 показывает зависимость экспрессии PD-1 от апоптотических изменений в опухоли яичников.

Ключевые слова: рак яичников, Ki-67, p53, PD-1/PD-L1.

 

Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов.

Вклад авторов

Разработка дизайна исследования: Журман В.Н., Плехова Н.Г.

Литературный поиск: Журман В.Н.

Сбор, анализ и интерпретация данных: Журман В.Н., Плехова Н.Г.

Написание и редактирование текста: Журман В.Н., Плехова Н.Г.

 

Литература

  1. Ishida Y., Agata Y., Shibahara K., Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992; 11 (11): 3887–3895. DOI: 10.1002/j.1460-2075.1992.tb05481.x.

  2. Zhu X., Jinghe L. The significance and therapeutic potential of PD-1 and its ligands in ovarian cancer: A systematic review. Gynecologic oncology. 2016; 142 (1): 184–189. DOI: 10.1016/j.ygyno.2016.04.002.

  3. Dong H., Zhu G., Tamada K., Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999; 5 (12): 1365–1369. DOI: 10.1038/70932.

  4. Кушлинский Н.Е., Герштейн Е.С., Горячева И.О. Растворимые формы рецептора контрольной точки иммунитета PD-1 и его лиганда PD-L1 в сыворотке крови больных почечно-клеточным раком: клинико-морфологические корреляции. Онкоурология. 2019; 15 (1): 15–22.

  5. Nishimura H., Honjo T., Minato N. Facilitation of beta selection and modification of positive selection in the thymus of PD-1-deficient mice. J. Exp Med. 2000; 191 (5): 891–898. DOI: 10.1084/jem.191.5.891.

  6. Guo X., Wang J., Jin J., Chen H., Zhen Z., Jiang W., Lin T., Huang H., Xia Z., Sun X. High Serum Level of Soluble Programmed Death Ligand 1 is Associated With a Poor Prognosis in Hodgkin Lymphoma. Translational oncology. 2018; 11 (3): 779–785. DOI: https://doi.org/10.1016/j.tranon.2018.03.012.

  7. Francisco L.M., Salinas V.H., Brown K.E., Vanguri V.K., Freeman G.J., Kuchroo V.K., Sharpe A.H. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. The Journal of experimental medicine. 2009; 206 (13): 3015–3029. DOI: https://doi.org/10.1084/jem.20090847.

  8. Sayapina M.S. Immunoregulatory functions of PD-1/PD-L1 inhibitors and development of resistance to them. Malignant Tumors. 2017; 2: 94–99.

  9. Gadducci Angiolo, Maria Elena Guerrieri. Immune Checkpoint Inhibitors in Gynecological Cancers: Update of Literature and Perspectives of Clinical Research. Anticancer research. 2017; 37 (11): 5955–5965. DOI: 10.21873/anticanres.12042.

  10. Rosenwald A., Wright G., Leroy K., Yu X., Gaulard P., Gascoyne R.D., Chan W.C., Zhao T., Haioun C., Greiner T.C., Weisenburger D.D., Lynch J.C., Vose J., Armitage J.O., Smeland E.B., Kvaloy S., Holte H., Delabie J., Campo E., Montserrat E., Staudt L.M. Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. The Journal of experimental medicine. 2003; 198 (6): 851–862. DOI: https://doi.org/10.1084/jem.20031074.

  11. Maleki V.S., Garrigos C., Duran I. Biomarkers of response to PD-1/PD-L1 inhibition. Crit Rev Oncol Hematol. 2017; 116: 116–124. DOI: 10.1016/j.critrevonc.2017.06.001.

  12. Yuasa T., Masuda H., Yamamoto S., Numao N., Yonese J. Biomarkers to predict prognosis and response to checkpoint inhibitors. Int J Clin Oncol. 2017; 22 (4): 629–634. DOI: 10.1007/s10147-017-1122-1.

  13. Huang X., Zhang W., Zhang Z., Shi D., Wu F., Zhong B., Shao Z. Prognostic Value of Programmed Cell Death 1 Ligand-1 (PD-L1) or PD-1 Expression in Patients with Osteosarcoma: A Meta-Analysis. Journal of Cancer. 2018; 9 (14): 2525–2531. DOI: https://doi.org/10.7150/jca.25011.

  14. Kim K.S., Sekar R.R., Patil D., Dimarco M.A., Kissick H.T., Bilen M.A., Osunkoya A.O., Master V.A. Evaluation of programmed cell death protein 1 (PD-1) expression as a prognostic biomarker in patients with clear cell renal cell carcinoma. Oncoimmunology. 2018; 7 (4): e1413519. DOI: https://doi.org/ 10.1080/2162402X.2017.1413519.

  15. Sacher A.G., Leena G. Biomarkers for the Clinical Use of PD-1/PD-L1 Inhibitors in Non-Small-Cell Lung Cancer: A Review. JAMA oncology. 2016; 2 (9): 1217–1222. DOI: 10.1001/jamaoncol.2016.0639.

  16. Darb-Esfahani S., Kunze C.A., Kulbe H., Sehouli J., Wienert S., Lindner J., Budczies J., Bockmayr M., Dietel M., Denkert C., Braicu I., Jöhrens K. Prognostic impact of programmed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor-infiltrating lymphocytes in ovarian high grade serous carcinoma. Oncotarget. 2016; 7 (2): 1486–1499. DOI: https://doi.org/10.18632/oncotarget.6429.

  17. Drakes M.L., Mehrotra S., Aldulescu M., Potkul R.K., Liu Y., Grisoli A., Joyce C., O'Brien T.E., Stack M.S., Stiff P.J. Stratification of ovarian tumor pathology by expression of programmed cell death-1 (PD-1) and PD-ligand-1 (PD-L1) in ovarian cancer. Journal of ovarian research. 2018; 11 (1): 43. DOI: https://doi.org/10.1186/s13048-018-0414-z.

  18. Strickland K.C., Howitt B.E., Shukla S.A., Rodig S., Ritterhouse L.L., Liu J.F., Garber J.E., Chowdhury D., Wu C.J., D'Andrea A.D., Matulonis U.A., Konstantinopoulos P.A. Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer. Oncotarget. 2016; 7 (12): 13587–13598. DOI: https://doi.org/10.18632/oncotarget.7277.

  19. Wieser V., Gaugg I., Fleischer M., Shivalingaiah G., Wenzel S., Sprung S., Lax S.F., Zeimet A.G., Fiegl H., Marth C. BRCA1/2 and TP53 mutation status associates with PD-1 and PD-L1 expression in ovarian cancer. Oncotarget. 2018; 9 (25): 17501–17511. DOI: https://doi.org/10.18632/oncotarget.24770.

  20. Inayama Y., Hamanishi J., Matsumura N., Murakami R., Abiko K., Yamaguchi K., Baba T., Horie K., Konishi I., Mandai M. Antitumor Effect of Nivolumab on Subsequent Chemotherapy for Platinum-Resistant Ovarian Cancer. The oncologist. 2018; 23 (11): 1382–1384. DOI: https://doi.org/10.1634/theoncologist.2018-0167.

  21. Zhu X., Xu J., Cai H., Lang J. Carboplatin and programmed death-ligand 1 blockade synergistically produce a similar antitumor effect to carboplatin alone in murine ID8 ovarian cancer model. J Obstet Gynaecol Res. 2018; 44 (2): 303–311. DOI: 10.1111/jog.13521.

  22. Юдина А.С., Абизяева И.Л., Юдин С.В., Жерновой М.В. Организационные проблемы профилактической онкологии органов репродуктивной системы женщин. Тихоокеанский медицинский журнал. 2007; 4: 83–84.

  23. Mittendorf E.A., Philips A.V., Meric-Bernstam F., Qiao N., Wu Y., Harrington S., Su X., Wang Y., Gonzalez-Angulo A.M., Akcakanat A., Chawla A., Curran M., Hwu P., Sharma P., Litton J. K., Molldrem J.J., Alatrash G. PD-L1 expression in triple-negative breast cancer. Cancer immunology research. 2014; 2 (4): 361–370. DOI: https://doi.org/10.1158/2326-6066.CIR-13-0127.

  24. Wimberly H., Brown J.R., Schalper K., Haack H., Silver M.R., Nixon C., Bossuyt V., Pusztai L., Lannin D.R., Rimm D.L. PD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer. Cancer immunology research. 2015; 3 (4): 326–332. DOI: https://doi.org/10.1158/2326-6066.CIR-14-0133.

  25. Ding Y., Sun C., Li J., Hu L., Li M., Liu J., Pu L., Xiong S. The Prognostic Significance of Soluble Programmed Death Ligand 1 Expression in Cancers: A Systematic Review and Meta-analysis. Scandinavian journal of immunology. 2017; 86 (5): 361–367. DOI: https://doi.org/10.1111/sji.12596.

  26. Theodoraki M.N., Yerneni S.S., Hoffmann T.K., Gooding W.E., Whiteside T.L. Clinical Significance of PD-L1+ Exosomes in Plasma of Head and Neck Cancer Patients. Clin Cancer Res. 2018; 24 (4): 896–905. DOI: 10.1158/1078-0432.CCR-17-2664.

  27. Wei W., Xu B., Wang Y., Wu C., Jiang J., Wu C. Prognostic significance of circulating soluble programmed death ligand-1 in patients with solid tumors: A meta-analysis. Medicine (Baltimore). 2018; 97 (3): e9617. DOI: 10.1097/MD.0000000000009617.

 

Поступила в редакцию 01.11.2022; принята 05.04.2023.

 

Авторский коллектив

Журман Варвара Николаевна – кандидат медицинских наук, врач-онколог, ГБУЗ «Приморский краевой онкологический диспансер». 690000, Россия, г. Владивосток, ул. Русская, 63А; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: http://orcid.org/0000-0002-6927-3336

Плехова Наталья Геннадьевна – доктор биологических наук, заведующая Центральной научно-исследовательской лабораторией, профессор кафедры клинической лабораторной диагностики, общей и клинической иммунологии, ФГБОУ ВО «Тихоокеанский государственный медицинский университет» Министерства здравоохранения Российской Федерации. 690002, г. Владивосток, пр-т Острякова, 2; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: http://orcid.org/0000-0002-8701-7213

 

Образец цитирования

Журман В.Н., Плехова Н.Г. Экспрессия рецептора к белку программированной гибели клеток PD-1 и его лиганда PD-L1 при серозном раке яичников high-grade. Ульяновский медико-биологический журнал. 2023; 3: 95–108. DOI: 10.34014/2227-1848-2023-3-95-108.