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Dynamics of Soluble Forms of the Immune Checkpoint Components PD-1/PD-L1/B7-H3, CD314/ULBP1, and HLA-G in Peripheral Blood of Melanoma Patients Receiving Blockers of Programmed Cell Death Protein PD-1

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The content of the soluble forms of immune checkpoint components sPD-1, sPD-L1 in blood serum, and sB7-H3, sCD314, sULBP1, sHLA-G in blood plasma of 30 melanoma patients receiving immunotherapy with anti-PD-1 antibodies (nivolumab, pembrolisumab) was measured before and in 4 and 8 weeks after the start of immunotherapy. The control group comprised 70 practically healthy donors. Standard immunoassay kits were used. In melanoma patients, the levels of sPD-L1 and sB7-H3 were significantly higher than in the control group (p<0001), sPD-1 level did not differ from the control, while sCD314 and sHLA-G levels were insignificantly decreased. During therapy, opposite changes in the levels of markers in individual patients were observed, and frequently after the initial increase (or decrease) after the first 4 weeks normalization did occur in the further 4 weeks. No statistically significant associations between the initial levels of markers and direction of their changes during treatment were found, but some trends indicating to the potential benefits from assessment of soluble forms of immune checkpoint proteins for evaluation and monitoring of the efficiency of the therapy with immune checkpoint blockers were revealed: significant decrease of sB7-H3 and sPD-1 levels in the course of treatment, higher initial sPD-1 level in patients with future progression than in those with stabilization or partial effect, and lower progression frequency in patients with increasing sPD-1 and sPD-L1 levels than in those with decreasing markers levels.

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References

  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. https://doi.org/10.17650/1726-9776-2018-14-2-54-67

  2. Alferov AA, Efimova MM, Kuzmin YuB, Kuznetsov IN, Gershtein ES, Kushlinskii NE. Key immune checkpoints and their inhibitors in the therapy of bone tumors. Part 2. Additional targets for immunotherapy of bone tumors and markers of its efficiency. Tekhnol. Zhivykh Sistem. 2021;18(1):18-31. Russian. https://doi.org/10.18127/j20700997-202101-02

  3. Huang FX, Wu JW Cheng XQ, Wang JH, Wen XZ, Li JJ, Zhang Q, Jiang H, Ding QY, Zhu XF, Zhang XS, Ding Y, Li DD. HHLA2 predicts improved prognosis of anti-PD-1/PD-L1 immunotherapy in patients with melanoma. Front. Immunol. 2022;13:902167. https://doi.org/10.3389/fimmu.2022.902167

  4. Yu J, Wu X, Song J, Zhao Y, Li H, Luo M, Liu X. Loss of MHC-I antigen presentation correlated with immune checkpoint blockade tolerance in MAPK inhibitor-resistant melanoma. Front. Pharmacol. 2022;13:928226. https://doi.org/10.3389/fphar.2022.928226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Gellrich FF, Schmitz M, Beissert S, Meier F. Anti-PD-1 and Novel Combinations in the Treatment of Melanoma-An Update. J. Clin. Med. 2020;9(1):223. https://doi.org/10.3390/jcm9010223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Topalian SL, Taube JM, Anders RA, Pardoll DM. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat. Rev. Cancer. 2016;16(5):275-287. https://doi.org/10.1038/nrc.2016.36

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ning B, Liu Y, Wang M, Li Y, Xu T, Wei Y. The Predictive Value of Tumor Mutation Burden on Clinical Efficacy of Immune Checkpoint Inhibitors in Melanoma: A Systematic Review and Meta-Analysis. Front. Pharmacol. 2022;13:748674. https://doi.org/10.3389/fphar.2022.748674

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. 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. https://doi.org/10.1097/MD.0000000000009617

    Article  PubMed  PubMed Central  Google Scholar 

  9. Zhou J, Mahoney KM, Giobbie-Hurder A, Zhao F, Lee S, Liao X, Rodig S, Li J, Wu X, Butterfield LH, Piesche M, Manos MP, Eastman LM, Dranoff G, Freeman GJ, Hodi FS. Soluble PD-L1 as a Biomarker in Malignant Melanoma Treated with Checkpoint Blockade. Cancer Immunol. Res. 2017;5(6):480-492. https://doi.org/10.1158/2326-6066.CIR-16-0329.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Carlino MS, Larkin J, Long GV. Immune checkpoint inhibitors in melanoma. Lancet. 2021;398:1002-1014. https://doi.org/10.1016/S0140-6736(21)01206-X

    Article  CAS  PubMed  Google Scholar 

  11. Bersanelli M, Petrelli F, Buti S, Stanganelli I. Immune checkpoint inhibitors in adjuvant setting after radical resection of melanoma: a meta-analysis of the pivotal trials. Hum. Vaccin. Immunother. 2022;18(3):1902723. https://doi.org/10.1080/21645515.2021

    Article  PubMed  Google Scholar 

  12. Aroldi F, Middleton MR. Long-Term Outcomes of Immune Checkpoint Inhibition in Metastatic Melanoma. Am. J. Clin. Dermatol. 2022;23(3):331-338. https://doi.org/10.1007/s40257-022-00681-4

    Article  PubMed  Google Scholar 

  13. Nebhan CA, Johnson DB. Predictive biomarkers of response to immune checkpoint inhibitors in melanoma. Expert Rev. Anticancer Ther. 2020;20(2):137-145. https://doi.org/10.1080/14737140.2020.1724539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Singh L, Singh MK, Kenney MC, Jager MJ, Rizvi MA, Meel R, Lomi N, Bakhshi S, Sen S, Kashyap S. Prognostic significance of PD-1/PD-L1 expression in uveal melanoma: correlation with tumor-infiltrating lymphocytes and clinicopathological parameters. Cancer Immunol. Immunother. 2021;70(5):1291-1303. https://doi.org/10.1007/s00262-020-02773-8

    Article  CAS  PubMed  Google Scholar 

  15. Yuan B, Miao L, Mei D, Li L, Zhou Q, Dong D, Wang S, Zhu X, Xu S. Value of a Signature of Immune-Related Genes in Predicting the Prognosis of Melanoma and Its Responses to Immune Checkpoint Blocker Therapies. Comput. Math. Methods Med. 2022;2022:9633416. https://doi.org/10.1155/2022/9633416

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, Russia

    E. S. Gershtein, E. A. Korotkova, E. V. Samoilova, O. I. Vashketova, Yu.B. Kuz’min, N. Yu. Sokolov & N. E. Kushlinskii

  2. AO GK MEDSI, MEDSI Clinical Hospital in Otradnoe, Krasnogorsk, Russia

    A. S. Mochalova

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  1. E. S. Gershtein
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  2. A. S. Mochalova
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  3. E. A. Korotkova
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  4. E. V. Samoilova
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  5. O. I. Vashketova
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  6. Yu.B. Kuz’min
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  7. N. Yu. Sokolov
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  8. N. E. Kushlinskii
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Correspondence to E. S. Gershtein.

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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 175, No. 4, pp. 482-487, April, 2023

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Gershtein, E.S., Mochalova, A.S., Korotkova, E.A. et al. Dynamics of Soluble Forms of the Immune Checkpoint Components PD-1/PD-L1/B7-H3, CD314/ULBP1, and HLA-G in Peripheral Blood of Melanoma Patients Receiving Blockers of Programmed Cell Death Protein PD-1. Bull Exp Biol Med 175, 481–486 (2023). https://doi.org/10.1007/s10517-023-05891-2

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