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Expression of Programmed Death-1 Ligands (PD-L1 and PD-L2) in Endometrial Carcinoma: Immunohistochemical Study
Passant Essam Shibel1, Reem R Mamdouh2, Maha E Salama1
1Department of Pathology, Faculty of Medicine, Cairo University, Egypt.
Background:
On basis of knowledge about the relationship between the immunity and cancer; cancer immunotherapies were introduced. Immune checkpoint regulators rank among the most crucial of those tactics. Programmed Death Ligand-1 (PD-L1) and Programmed Death Ligand-2 (PD-L2) are 2 ligands of Programmed Death-1 (PD-1); an immune checkpoint regulator. PD-L1 and PD-L2 antibodies have been effective in treating a variety of malignancies in clinical trials. Few of these antibodies have been approved for clinical use by the Food and Drug Administration (FDA). The purpose of this study was to assess the immunohistochemical expression of PD-L1 and PD-L2 by tumor cells (TC) and tumoral stroma immune cells (IC) in endometrial carcinoma (EC) and their association with the tumor's clinico-pathologic characteristics.
Material And Methods:
For 62 EC cases, PD-L1 and PD-L2 immunohistochemical expression was examined in the TC and IC.
Results:
Positive TC PD-L1 (25.8% of cases) was linked to high stromal tumor infiltrating lymphocytes (TILs) and high tumor grade. High TC PD-L2 (33.9% cases) was associated with non-endometrioid types, high tumor grade, and high FIGO stage. Positive IC PD-L1 (51.6% of cases) was correlated to non-endometrioid types, high tumor grade, high FIGO stage and high stromal TILs. High IC PD-L2 expression (14.5% of cases) was associated with lympho-vascular space invasion. Both PD-L1 and PD-L2 expression in both TC and IC were found to be directly correlated. Crucially, some of the PD-L1 negative cases had significant expression of PD-L2.
Conclusion:
Our results supported PD-L1 & PD-L2 expression in EC, particularly in high grade, high FIGO stage, non-endometrioid and TILs rich tumors, highlighting such cases as candidates for anti- PD-1 therapy. Furthermore, the identification of PD-L2 positive PD-L1 negative cases may indicate the combination of PD-L1 and PD-L2 testing to nominate cases that may benefit from the PD-1 pathway targeting therapies.
Insights
Programmed Death Ligand-1 (PD-L1) and Programmed Death Ligand-2 (PD-L2) are expressed in endometrial carcinoma (EC). High expression of PD-L1 and PD-L2 in EC is linked to advanced tumor characteristics and suggests potential benefit from anti-PD-1 therapies.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Cancer immunotherapies leverage the relationship between immunity and cancer.
- Immune checkpoint regulators, such as Programmed Death-1 (PD-1) and its ligands PD-L1 and PD-L2, are crucial targets.
- PD-1 pathway antibodies show promise in treating various cancers, with some FDA-approved.
Purpose of the Study:
- To investigate the immunohistochemical expression of PD-L1 and PD-L2 in tumor cells (TC) and immune cells (IC) within endometrial carcinoma (EC).
- To correlate PD-L1 and PD-L2 expression with clinico-pathologic characteristics of EC.
Main Methods:
- Examined PD-L1 and PD-L2 immunohistochemical expression in tumor cells (TC) and tumoral immune cells (IC).
- Analyzed data from 62 endometrial carcinoma cases.
Main Results:
- Positive tumor cell PD-L1 expression correlated with high tumor grade and stromal tumor-infiltrating lymphocytes (TILs).
- High tumor cell PD-L2 expression was associated with non-endometrioid types, high tumor grade, and high FIGO stage.
- Positive immune cell PD-L1 expression linked to non-endometrioid types, high tumor grade, high FIGO stage, and high stromal TILs; high immune cell PD-L2 expression correlated with lympho-vascular space invasion.
- Direct correlation observed between PD-L1 and PD-L2 expression in both TC and IC; notable PD-L2 expression found in PD-L1 negative cases.
Conclusions:
- PD-L1 and PD-L2 expression is present in EC, particularly in high-grade, high-stage, non-endometrioid, and TILs-rich tumors.
- These findings highlight EC cases with specific characteristics as candidates for anti-PD-1 therapy.
- Testing for both PD-L1 and PD-L2 may be beneficial for identifying patients who could gain from PD-1 pathway-targeting treatments.
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