Advertisement

Soluble Ligand of the Immune Checkpoint Receptor (sPD-L1) in Blood Serum of Patients with Renal Cell Carcinoma

  • N. E. KushlinskiiEmail author
  • E. S. Gershtein
  • A. A. Morozov
  • I. O. Goryacheva
  • M. L. Filipenko
  • A. A. Alferov
  • S. D. Bezhanova
  • V. V. Bazaev
  • I. A. Kazantseva
Article
  • 7 Downloads

The content of the soluble ligand of the immune checkpoint receptor (sPD-L1) was determined in the blood serum of 106 patients with renal cell carcinoma and 11 patients with benign kidney tumors by direct ELISA (Human sPD-L1 Platinum ELISA; Affimetrix, eBioscience). The control group included 19 healthy men and 18 women. Serum level of sPD-L1 significantly surpassed the control values in both patients with primary renal cancer (p<0.0001) and in patients examined during disease progression (p<0.05). In patients with benign kidney tumors, the level of this marker was significantly higher than in the control (p<0.05), but lower than in patients with renal cell carcinoma. The sPD-L1 level significantly increased with disease stage (p<0.001); it was higher in the presence of metastases in regional lymph nodes irrespective of their number (N1 or N2) than in the absence of metastases (N0); it was also increased in patients with distant metastases (M1) and patients with grade III-IV tumors in comparison with grade III-IV tumors (p<0.05). The highest sPD-L1 levels were recorded in patients with tumor size corresponding to T2 and T3 and decreased in patients with T4 tumors. Thus, sPD-L1 level in patients with renal cell carcinoma correlated with tumor grade and metastasizing and can be considered as a promising marker in monitoring of the effect of anti-PD1/PD-L1 therapy.

Key Words

immune checkpoint proteins sPD-L1 renal cell carcinoma blood serum 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Kushlinskii NE, Fridman MV, Morozov AA, Gershtein ES, Kadagidze ZG, Matveev VB. Modern approaches to kidney cancer immunotherapy. Onkourologiya. 2018;14(2):54-67. Russian.CrossRefGoogle Scholar
  2. 2.
    Alessi C, Scapulatempo Neto C, Viana CR, Vazquez VL. PD-1/PD-L1 and VEGF-A/VEGF-C expression in lymph node microenvironment and association with melanoma metastasis and survival. Melanoma Res. 2017;27(6):565-572.CrossRefGoogle Scholar
  3. 3.
    Chen Y, Wang Q, Shi B, Xu P, Hu Z, Bai L, Zhang X. Development of a sandwich ELISA for evaluating soluble PD-L1 (CD274) in human sera of different ages as well as supernatants of PD-L1+ cell lines. Cytokine. 2011;56(2):231-238.CrossRefGoogle Scholar
  4. 4.
    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.CrossRefGoogle Scholar
  5. 5.
    Frigola X, Inman BA, Lohse CM, Krco CJ, Cheville JC, Thompson RH, Leibovich B, Blute ML, Dong H, Kwon ED. Identification of a soluble form of B7-H1 that retains immunosuppressive activity and is associated with aggressive renal cell carcinoma. Clin. Cancer Res. 2011;17(7):1915-1923.CrossRefGoogle Scholar
  6. 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. Transl. Oncol. 2018;11(3):779-785.CrossRefGoogle Scholar
  7. 7.
    Hamanishi J, Mandai M, Matsumura N, Abiko K, Baba T, Konishi I. PD-1/PD-L1 blockade in cancer treatment: perspectives and issues. Int. J. Clin. Oncol. 2016;21(3):462-473.CrossRefGoogle Scholar
  8. 8.
    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 metaanalysis. J. Cancer. 2018;9(14):2525-2531.CrossRefGoogle Scholar
  9. 9.
    Kim KS, Sekar RR, Patil D, Dimarco MA, Kissick HT, Bilen MA, Osunkoya AO, Master VA. 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.CrossRefGoogle Scholar
  10. 10.
    Massari F, Santoni M, Ciccarese C, Santini D, Alfieri S, Martignoni G, Brunelli M, Piva F, Berardi R, Montironi R, Porta C, Cascinu S, Tortora G. PD-1 blockade therapy in renal cell carcinoma: current studies and future promises. Cancer Treat. Rev. 2015;41(2):114-121.CrossRefGoogle Scholar
  11. 11.
    Sacher AG, Gandhi L. Biomarkers for the clinical use of PD-1/PD-L1 inhibitors in non-small-cell lung cancer: a review. JAMA Oncol. 2016;2(9):1217-1222.CrossRefGoogle Scholar
  12. 12.
    Theodoraki MN, Yerneni SS, Hoffmann TK, Gooding WE, 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.CrossRefGoogle Scholar
  13. 13.
    Topalian SL, Taube JM, Anders RA, Pardoll DM. Mechanismdriven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat. Rev. Cancer. 2016;16(5):275-287.CrossRefGoogle Scholar
  14. 14.
    Tsang JY, Au WL, Lo KY, Ni YB, Hlaing T, Hu J, Chan SK, Chan KF, Cheung SY, Tse GM. PD-L1 expression and tumor infiltrating PD-1+ lymphocytes associated with outcome in HER2+ breast cancer patients. Breast Cancer Res. Treat. 2017;162(1):19-30.CrossRefGoogle Scholar
  15. 15.
    Zhu X, Lang J. Soluble PD-1 and PD-L1: predictive and prognostic significance in cancer. Oncotarget. 2017;8(57):97 671-97 682.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • N. E. Kushlinskii
    • 1
    Email author
  • E. S. Gershtein
    • 1
  • A. A. Morozov
    • 2
  • I. O. Goryacheva
    • 1
  • M. L. Filipenko
    • 3
  • A. A. Alferov
    • 1
  • S. D. Bezhanova
    • 1
  • V. V. Bazaev
    • 2
  • I. A. Kazantseva
    • 2
  1. 1.N. N. Blokhin National Medical Research Center of OncologyMinistry of Health of the Russian FederationMoscowRussia
  2. 2.M. F. Vladimirsky Moscow Regional Research Clinical InstituteMoscowRussia
  3. 3.Institute of Chemical Biology and Fundamental MedicineSiberian Division of the Russian Academy of SciencesNovosibirskRussia

Personalised recommendations