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

S.S. Salamatin; E.S. Gershtein; A.N. Khakimov; E.I. Karamysheva; T.N. Zabotina; N.E. Kushlinskii

doi:10.18127/j20700997-202601-03

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

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

research article UDC 618.19-006.6-074:615.383 Pages: 31-38 doi.org/10.18127/j20700997-202601-03

^1,4 Russian University of Medicine Ministry of Health of the Russian Federation (Moscow, Russia)
^2,6 Russian University of Medicine Ministry of Health of the Russian Federation (Moscow, Russia); N.N. Blokhin National Medical Research Center of Oncology
^3,5 N.N. Blokhin National Medical Research Center of Oncology

Keywords: Breast cancer sPD-1 sPD-L1 blood serum

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.

Received: 12.11.2025
Approved after review: 12.11.2025
Accepted: 25.12.2025

How to cite

Саламатин С.С., Герштейн Е.С., Хакимов А.Н., Карамышева Е.И., Заботина Т.Н., Кушлинский Н.Е. Растворимые формы рецептора PD-1 и его лиганда PD-L1 в сыворотке крови больных раком молочной железы и их связь с клиническими и морфологическими особенностями заболевания // Технологии живых систем. 2026. № 1. С. 31–38. DOI: https://doi.org/10.18127/j20700997-202601-03

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[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

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