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Updated: May 24, 2025
Author Spotlight: Advancing Reproductive Immunology with a Protocol for the Quantitative Evaluation of Endometrial Immune Cells
Published on: October 13, 2023
Gene expression and soluble protein level of PD-1 and its ligands (PD-L1 and PD-L2) in endometrial cancer
Mohd Nazzary Mamat Yusof1, Kah Teik Chew1, Nirmala Chandralega Kampan1
1Department of Obstetrics and Gynaecology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Abstract:
Checkpoint programmed death-1 (PD-1) and programmed cell death ligands (PD-Ls) are negative immunoregulatory molecules that assist tumour cells in evading the immune system. The interaction of PD-1 and PD-Ls inhibits T cells and tumour-infiltrating lymphocytes (TILs) while increasing the function of immunosuppressive regulatory T cells (Tregs). This leads to the evasion of the immune response by tumour cells. The roles of PD-1, PD-L1, and PD-L2 in endometrial cancer (EC) have not been fully elucidated. This study investigates the mRNA gene expression and soluble protein levels of these molecules in EC compared to controls, with detailed analysis of clinical profiles. The results showed that EC had significantly higher mRNA gene expression and soluble protein levels of PD-L1 and PD-L2, but not PD-1. Specifically, PD-1 mRNA gene expression was significantly higher in cases with less than 50% myometrial invasion. Additionally, the soluble protein level of PD-1 was substantially higher in patients under the age of 60. Higher gene expression of PD-L1 was observed only in advanced stages of EC. However, the soluble PD-L1 protein level was significantly elevated in type II EC, advanced stage, higher grade, lympho-vascular space invasion (LVSI), and in cases with myometrial invasion of 50% or more. PD-L2 mRNA gene expression and soluble protein levels significantly differed across all clinical profiles except for LVSI. These findings suggest that PD-1, PD-L1, and PD-L2 may serve as potential predictive biomarkers, which could be beneficial for the management of endometrial cancer patients through immunotherapy.
Insights
Endometrial cancer (EC) shows higher levels of programmed cell death ligand 1 (PD-L1) and PD-L2, suggesting they may be biomarkers for immunotherapy. PD-1 levels varied with clinical factors.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Programmed death-1 (PD-1) and its ligands (PD-Ls) are key regulators of immune responses, often exploited by tumors to evade immune surveillance.
- The interaction between PD-1 and PD-Ls suppresses T cell activity and promotes immunosuppressive cells, facilitating tumor immune evasion.
- The specific roles and expression patterns of PD-1, PD-L1, and PD-L2 in endometrial cancer (EC) remain incompletely understood.
Purpose of the Study:
- To investigate the mRNA gene expression and soluble protein levels of PD-1, PD-L1, and PD-L2 in endometrial cancer (EC) tissues and compare them to control samples.
- To analyze the correlation between the expression of these molecules and various clinical profiles in EC patients.
Main Methods:
- Quantitative analysis of mRNA gene expression for PD-1, PD-L1, and PD-L2.
- Measurement of soluble protein levels for PD-1, PD-L1, and PD-L2.
- Correlation analysis with clinical parameters including tumor stage, grade, myometrial invasion, and lympho-vascular space invasion (LVSI).
Main Results:
- Endometrial cancer exhibited significantly higher mRNA and soluble protein levels for PD-L1 and PD-L2 compared to controls, but not for PD-1.
- PD-1 mRNA levels were higher in EC with less than 50% myometrial invasion, and soluble PD-1 protein was higher in patients under 60.
- Soluble PD-L1 protein levels were significantly elevated in type II EC, advanced stages, higher grades, with LVSI, and deeper myometrial invasion (≥50%). PD-L2 expression differed across most clinical profiles.
Conclusions:
- PD-L1 and PD-L2 are upregulated in endometrial cancer and show distinct correlations with clinical parameters.
- The expression patterns of PD-1, PD-L1, and PD-L2 suggest their potential as predictive biomarkers for immunotherapy in EC.
- Further research is warranted to explore the therapeutic implications of targeting the PD-1/PD-L pathway in endometrial cancer management.
