500 rub
Journal Technologies of Living Systems №1 for 2026 г.
Article in number:
Soluble forms of the PD-1 receptor and its ligand PD-L1 in the blood serum of breast cancer patients and their relationship with clinical and morphological features of the disease
Type of article: scientific article
DOI: https://doi.org/10.18127/j20700997-202601-03
UDC: 618.19-006.6-074:615.383
Authors:

S.S. Salamatin1, E.S. Gershtein2, A.N. Khakimov3, E.I. Karamysheva4, T.N. Zabotina5, N.E. Kushlinskii6

1,2,4,6 Russian University of Medicine Ministry of Health of the Russian Federation (Moscow, Russia)

2,3,5,6 N.N. Blokhin National Medical Research Center of Oncology

Ministry of Health of the Russian Federation (Moscow, Russia)

1 salamatinsergey26@yandex.ru, 2 esgershtein@gmail.com, 3 salamakbar97@mail.ru, 4 prof.karamysheva@gmail.com, 5 tatzabotina@yandex.ru, 6 kne3108@gmail.com

Abstract:

The aim of this study was to analyze the levels of soluble PD-1 (sPD-1) and PD-L1 (sPD-L1) in blood serum of breast cancer patients and their association with clinical and morphological characteristics of the disease. The study included 84 patients with breast cancer (stages IIa-IIIc, mean age 52 years) and 49 healthy women (control group, mean age 48 years). Serum sPD-1 and sPD-L1 concentrations were determined using an enzyme-linked immunosorbent assay before the start of specific treatment. A statistically significant decrease in sPD-1 levels and an increase in sPD-L1 concentrations were observed in patients with breast cancer compared to the control group (p<0.0001). A positive correlation was found between sPD-1 and sPD-L1 levels in breast cancer patients (R = 0.41; p<0.001) and no correlation in the control group. sPD-1 levels remained relatively stable across all disease stages, while sPD-L1 demonstrated high variability, particularly at stage IIIb (T4N1/2M0) where concentrations ranged from 1.57 to 527 pg/mL. These data confirm the important role of the PD-1/PD-L1 system in the pathogenesis of breast cancer. The results have potential clinical significance for the development of prognostic criteria and a personalized approach to the use of immunotherapy in patients with breast cancer.

Pages: 31-38
References
  1. Zhukova L.G., Gevorkyan T.G. BREAST CANCER. Modern Oncology. 2021. V. 23. № 1. P. 5–40. URL: https://cyberleninka.ru/article/n/rak-molochnoy-zhelezy
  2. Riggio A.I., Varley K.E., Welm A.L. The lingering mysteries of metastatic recurrence in breast cancer. Br. J. Cancer. 2021. V. 124. № 1. P. 13–26. DOI: 10.1038/s41416-020-01161-4
  3. Salamatin S.S., Kovaleva O.V., Ryabchikov D.A. et al. Soluble forms of the programmed cell death receptor PD-1 and its ligand PD-L1 in breast cancer. Problems of biological, medical and pharmaceutical chemistry. 2024. V. 27. № 12. P. 3−9. DOI:10.29296/25877313-2024-12-00
  4. Aguirre J.E., Beswick E.J., Grim C. et al. Matrix metalloproteinases cleave membrane-bound PD-L1 on CD90+ (myo-)fibroblasts in Crohn’s disease and regulate Th1/Th17 cell responses. Int. Immunol. 2020. V. 32. № 1. P. 57–68. DOI: 10.1093/intimm/dxz060
  5. Spangenberg S.H., Palermo A., Gazaniga N.R. et al. Hydroxyproline metabolism enhances IFN-γ-induced PD-L1 expression and inhibits autophagic flux. Cell. Chem. Biol. 2023. V. 30. № 9. P. 1115–1134. DOI: 10.1016/j.chembiol.2023.06.016
  6. Hu S., He W., Wu G. Hydroxyproline in animal metabolism, nutrition, and cell signaling. Amino Acids. 2021. V. 54. № 4. P. 513–528. DOI: 10.1007/s00726-021-03056-x
  7. Kushlinskij N.E., Maslennikov V.V., Korotkova E.A. i dr. Soderzhanie rastvorimyh form receptora programmiruemoj gibeli kletki sPD-1 i ego liganda sPD-L1 v syvorotke krovi bol'nyh kolorektal'nym rakom. Tekhnologii zhivyh sistem. 2022. T. 19. № 2. S. 5−17. DOI: 10.18127/j20700997-202202-018 (in Russian).
  8. Yi M., Niu M., Xu L. et al. Regulation of PD-L1 expression in the tumor microenvironment. J. Hematol. Oncol. 2021. V. 14. № 1. P. 10. DOI: 10.1186/s13045-020-01027-5
  9. Lawler S.E., Nowicki M.O., Ricklefs F.L., Chiocca E.A. Immune escape mediated by exosomal PD-L1 in cancer. Adv. Biosyst. 2020. V. 4. № 12. P. 1–14. DOI: 10.1002/adbi.202000017
  10. Bailly C., Thuru X., Quesnel B. Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases. Cancers (Basel). 2021. V. 13. № 12. P. 1–24. DOI: 10.3390/cancers13123034
  11. Jin M., Fang J., Peng J. et al. PD-1/PD-L1 immune checkpoint blockade in breast cancer: research insights and sensitization strategies. Mol. Cancer. 2024. V. 23. № 1. P. 266. DOI: 10.1186/s12943-024-02176-8
  12. Schmid P., Adams S., Rugo H.S. et al. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N. Engl. J. Med. 2018. V. 379. № 22. P. 2108–2121. DOI: 10.1056/NEJMoa1809615
  13. Wong G.L., Manore S.G., Doheny D.L., Lo H.W. STAT family of transcription factors in breast cancer: Pathogenesis and therapeutic opportunities and challenges. Semin. Cancer Biol. 2022. V. 86. P. 84–106. DOI: 10.1016/j.semcancer.2022.08.003
  14. Wang R., He S., Long J. et al. Emerging therapeutic frontiers in cancer: insights into posttranslational modifications of PD-1/PD-L1 and regulatory pathways. Exper. Hematol. Oncol. 2024. V. 13. № 1. P. 1–46. DOI: 10.1186/s40164-024-00515-5
  15. Chen G., Huang A.C., Zhang W. et al. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature. 2018. V. 560. № 7718. P. 382–386. DOI: 10.1038/s41586-018-0392-8
  16. Cortes J., Rugo H.S., Cescon D.W. et al. Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer. N. Engl. J. Med. 2022. V. 387. № 3. P. 217–226. DOI: 10.1056/NEJMoa2202809
  17. Pu Y., Ji Q. Tumor-Associated Macrophages Regulate PD-1/PD-L1 Immunosuppression. Front. Immunol. 2022. V. 3. P. 874589. DOI: 10.3389/fimmu.2022.874589
Date of receipt: 12.11.2025
Approved after review: 12.11.2025
Accepted for publication: 25.12.2025