Assessment of the PD-1/PD-L1/PD-L2 Immune Checkpoints Pathway in Endometrial Cancer and Its Clinical Significance
by
, , , , , , ,
Karolina Włodarczyk-Ciekańska
1,*
,
Agnieszka Kwiatkowska-Makuch
2,
Anna Pawłowska-Łachut
1,
Wiktoria Skiba
1,
Dorota Suszczyk
1,
Jan Kotarski
1,
Paulina Pieniądz-Feculak
1,3,
Anna Pańczyszyn
4,
Anna Ignatowicz
5,
Rafał Tarkowski
2 and
Iwona Wertel
1
1
Independent Laboratory of Cancer Diagnostics and Immunology, Faculty of Medicine, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland
2
I Chair and Department of Oncological Gynecology and Gynaecology, Medical University of Lublin, 20-059 Lublin, Poland
3
Department of Virology and Immunology, Institute of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, 20-031 Lublin, Poland
4
Medical Department, Institute of Medical Sciences, University of Opole, Oleska 48, 45-052 Opole, Poland
5
Students’ Scientific Association, Independent Laboratory of Cancer Diagnostics and Immunology, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland
*
Author to whom correspondence should be addressed.
Cancers 2025, 17(21), 3485; https://doi.org/10.3390/cancers17213485
Submission received: 27 August 2025
/
Revised: 27 October 2025
/
Accepted: 28 October 2025
/
Published: 29 October 2025
(This article belongs to the Special Issue Molecular Biology, Diagnosis and Management of Endometrial Cancer)
Simple Summary
Endometrial cancer (EC) develops in an environment strongly modulated by the immune system, and changes in dendritic cells (mDCs and pDCs), and monocytes (MO) expressing PD-L1 and PD-L2 may influence disease progression. Our study demonstrated that EC patients have lower percentages of PD-L1-positive MO and pDCs, as well as PD-L2-positive MO and mDCs, compared to the control group. We also found changes in plasma levels of soluble forms of PD-1, PD-L1, and PD-L2, which correlated with tumor PD-L2 expression and clinical characteristics, such as BMI and disease FIGO stage.
Abstract
Background: Endometrial cancer is one of the most common female genital cancers and poses a significant clinical problem due to its increasing incidence and variable prognosis depending on the stage of the disease. The development of EC is largely dependent on interactions with the immune system, including immune checkpoints (ICPs) such as PD-1, PD-L1, and PD-L2. The aim of our study was to evaluate the PD-1/PD-L1/PD-L2 pathway in EC and its clinical significance. Methods: The analysis was performed by flow cytometry on myeloid and plasmacytoid dendritic cells and monocytes (MO) in peripheral blood (PB). The concentration of sPD-1, sPD-L1, and sPD-L2 in plasma was determined by ELISA. Additionally, PD-L1 and PD-L2 gene expression levels in tumor tissue (TT) were assessed using real-time polymerase chain reaction (qPCR). The obtained results were correlated with clinical data of EC patients. Results: Patients with EC had lower percentages of PD-L1-positive MO and pDCs, as well as PD-L2-positive MO and mDCs, compared with the control group. We observed accumulation of sPD-1 and lower levels of sPD-L1 and sPD-L2 in EC patients compared to the control group, with sPD-L2 correlating with PD-L2 gene expression level in the TT. Conclusions: The study results indicate a difference in the distribution of mDCs, pDCs, and MO with PD-L1/PD-L2 expression in EC patients. Reduced percentages of MO and DCs expressing PD-L1 and PD-L2, altered concentrations of soluble forms of these IPCs, and correlations with gene expression in TT suggest that dysregulation of this pathway may influence disease progression. Furthermore, the relationships between immunological parameters and clinical features such as BMI and FIGO stages suggest the potential use of these factors as diagnostic and prognostic biomarkers and the possibility of incorporating them into future therapeutic strategies. However, further studies are necessary to validate this hypothesis.
