CONTENT OF CONTROL POINTS OF THE IMMUNITY SPD-1 AND SPD-L1 IN THE BLOOD PLASMA OF OVARIAN CANCER PATIENTS

DOI: https://doi.org/10.29296/25877313-2020-05-05
Issue: 
5
Year: 
2020

D.O. Utkin Oncologist, Moscow City Oncological Hospital № 62 of the Department of Health of the City of Moscow (Istra) E-mail: utkindo@yandex.ru E.A. Korotkova Ph.D. (Biol.), Senior Research Scientist, N.N. Blokhin National Medical Research Center for Oncology of the Ministry of Health of Russia (Moscow) N.A. Petrikova Pathologist, Ryazan Regional Clinical Oncology Center (Ryazan) V.D. Ermilova Ph.D. (Med.), Leading Research Scientist, Department of Pathological Anatomy of Human Tumors, N.N. Blokhin National Medical Research Center for Oncology of the Ministry of Health of Russia (Moscow) M.M. Khulamkhanova Oncologist, N.N. Blokhin National Medical Research Center for Oncology of the Ministry of Health of Russia (Moscow) D.N. Kushlinsky Ph.D. (Med.), Senior Research Scientist, A.F. Tsyb Medical Radiological Scientific Center  branch of the Federal State Budgetary Institution National Medical Research Center for Radiology (Obninsk) N.Yu. Sokolov Ph.D. (Med.), N.N. Blokhin National Medical Research Center for Oncology of the Ministry of Health of Russia (Moscow) K.I. Zhordania Dr.Sc. (Med.),Professor, Department of Gynecology, N.N. Blokhin National Medical Research Center for Oncology of the Ministry of Health of Russia (Moscow) E.S. Gerstein Dr.Sc. (Biol.), Professor, Leading Research Scientist, N.N. Blokhin National Medical Research Center for Oncology of the Ministry of Health of Russia (Moscow)

Relevance. In recent years, close attention has been paid to the study of the expression of the PD-1 / PD-L1 signaling pathway in malignant tumors, including ovarian cancer (OC). The low effectiveness of the treatment of OC can be associated with various factors, including the mechanisms of the tumor escaping from the immune response through the PD-1 / PD-L1 immunity checkpoint system. Relatively recently, studies have appeared on the study of soluble forms of PD-1 and its ligands (sPD-1, sPD-L1 / 2) in the blood of cancer patients. These data are beginning to be actively used in an oncology clinic in the treatment of melanoma, renal cell carcinoma, non-small cell lung cancer. Purpose of the study. Analysis of the content of sPD-1 and sPD-L1 in the blood plasma of patients with OC, taking into account the main clinical and morphological characteristics of the disease. Material and methods. We examined 93 patients with OС, 22 with benign ovarian neoplasms, 10 with borderline ovarian tumors, and 35 with healthy women in the control group. In all, an ovarian tumor was detected for the first time and confirmed by histological examination. The concentra-tions of sPD-L1 and sPD-1 were determined in the blood plasma of patients and healthy women before the start of specific treatment using standard reagent kits for direct enzyme immunoassay Human PD-L1 Platinum ELISA and Human PD-1 ELISA kit (Affymetrix, eBioscience, USA) in accordance with the manufacturer's instructions. The reliability of the differences was evaluated using nonparametric tests (Mann-Whitney U-test, Kolmogorov-Smirnov type test). For all statistical tests, p values

Keywords: 
ovarian cancer
biomarkers
sPD-1
sPD-L1
blood plasma

References: 
  1. Ferlay J., Soerjomataram I., Dikshit R., Eser S., Mathers C., Rebelo M., Parkin D.M., Forman D., Bray F.Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer. 2015; 136(5):359–386.
  2. Korkmaz T., Seber S., Basaran G. Review of the current role of targeted therapies as maintenance therapies in first and second line treatment of epithelial ovarian cancer; in the light of completed trials. Crit. Rev. Oncol. Hematol. 2016; 98:180–188.
  3. Markman M., Liu P.Y., Wilczynski S., Monk B., Copeland L.J., Alvarez R.D., Jiang C., Alberts D.; Southwest Oncology Group; Gynecologic Oncology Group. Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy: a southwest oncology group and gynecologic oncology group trial. J. Clin. Oncol. 2003; 21(13):2460–2465.
  4. Mandai M., Hamanishi J., Abiko K., Matsumura N., Baba T., Konishi I. Anti-PD-L1/PD-1 immune therapies in ovarian cancer: basic mechanism and future clinical application. Int. J. Clin. Oncol. 2016; 21(3):456–461.
  5. Zhu X., Lang J. The significance and therapeutic potential of PD-1 and its ligands in ovarian cancer: A systematic review. Gynecol. Oncol. 2016; 142(1):184–189.
  6. 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. Oncologist. 2018; 23(11):1382–1384.
  7. Velcheti V., Schalper K.A., Carvajal D.E., Anagnostou V.K., Syrigos K.N., Sznol M., Herbst R.S., Gettinger S.N., Chen L., Rimm D.L. Programmed death ligand-1 expression in non-small cell lung cancer. Lab. Invest. 2014; 94(1):107–116.
  8. Hwang W.T., Adams S.F., Tahirovic E., Hagemann I.S., Coukos G.Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta-analysis. Gynecol. Oncol. 2012; 124(2):192–198.
  9. Hamanishi J., Mandai M., Konishi I. Immune checkpoint inhibition in ovariancancer. Int.Immunol.2016; 28(7):339–348.
  10. Zhu X., Lang J. Soluble PD-1 and PD-L1: predictive and prognostic significance in cancer. Oncotarget. 2017; 8(57):97671–97682.
  11. Chatterjee J., Dai W., Aziz N.H.A., Teo P.Y., Wahba J., Phelps D.L., Maine C.J., Whilding L.M., Dina R., Trevisan G., Flower K.J., George A.J.T., Ghaem-Maghami S. Clinical use of programmed cell death-1 and its ligand expression as discriminatory and predictive markers in ovarian cancer. Clin. Cancer Res. 2017; 23(13):3453–3460.
  12. 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. Transl. Oncol. 2018; 11(3):779–785.
  13. Kim H.J., Park S., Kim K.J., Seong J. Clinical significance of soluble programmed cell death ligand-1 (sPD-L1) in hepatocellular carcinoma patients treated with radiotherapy. Radiother. Oncol. 2018; 129(1):130–135.
  14. Theodoraki M.N., Yerneni S.S., Homann T.K., Gooding W.E., Whiteside T.L. Clinical signi - cance of PD-L1(+) exosomes in plasma of head and neck cancer patients. Clin. Cancer Res. 2018; 24(4):896–905.
  15. 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 // Scand. J. Immunol. 2017; 86(5):361–367.
  16. We 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):9617.
  17. Kushlinskiĭ N.E., Gershteĭn E.S., Morozov A.A., Gorjacheva I.O., Filipenko M.L., Alferov A.A., Bezhanova S.D., Bazaev V.V., Kazantseva I.A. Rastvorimyĭ ligand retseptora kontrol'noĭ tochki immuniteta (sPD-L1) v syvorotke krovi pri pochechno-kletochnom rake. Bjull. eksper. biol. med. 2018; 166(9):325–329. (Kushlinskii N.E., Gershtein E.S., Morozov A.A., Goryacheva I.O., Filipenko M.L., Alferov A.A., Bezhanova S.D., Bazaev V.V., Kazanceva I.A. Rastvorimyĭ ligand receptora kontrol'noĭ tochki immuniteta (sPD-L1) v syvorotke krovi pri pochechno-kletochnom rake. Byull. eksper. biol. med. 2018; 166(9):325–329. [In Russ.]).
  18. Zheng Z., Bu Z., Liu X., Zhang L., Li Z., Wu A., Wu X., Cheng X., Xing X., Du H., Wang X., Hu Y., Ji J. Level of circulating PD-L1 expression in patients with advanced gastric cancer and its clinical implications. Chin. J. Cancer Res. 2014; 26(1):104–111.
  19. Finkelmeier F., Canli O., Tal A., Pleli T., Trojan J., Schmidt M., Kronenberger B., Zeuzem S., Piiper A., Greten F.R., Waidmann O. High levels of the soluble programmed death-ligand (sPD-L1) identify hepatocellular carcinoma patients with a poor prognosis. Eur. J. Cancer. 2016; 59:152–159.
  20. Zhang J., Gao J., Li Y., Nie J., Dai L., Hu W., Chen X., Han J., Ma X., Tian G., Wu D., Shen L., Fang J. Circulating PD-L1 in NSCLC patients and the correlation between the level of PD-L1 expression and the clinical characteristics. Thorac. Cancer. 2015; 6(4):534–538.