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KMID : 1137020230340020018
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Journal of Gynecologic Oncology
2023 Volume.34 No. 2 p.18 ~ p.18
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Lymphocyte activation gene (LAG)-3 is a potential immunotherapeutic target for microsatellite stable, programmed death-ligand 1 (PD-L1)-positive endometrioid endometrial cancer
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Hong Jin-Hwa
Cho Hyun-Woong
Ouh Yung-Taek
Lee Jae-Kwan
Chun Yi-Kyeong
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Abstract
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Objective: Immune checkpoint inhibitors have been widely used in the treatment of endometrial cancer (EC) with microsatellite instability-hypermutated (MSI-H). However, there is an unmet need for microsatellite stable (MSS) EC because of their modest activity. This study aimed to identify potential immune-related biomarkers in MSS EC.
Methods: One hundred and twenty-three patients with EC who underwent hysterectomy were enrolled. MSI status was determined using MSI analysis and/or immunohistochemical staining for mismatch repair proteins. Immunohistochemical analysis of programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), PD-L2, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), cluster of differentiation 3 (CD3), CD8, lymphocyte activation gene-3 (LAG-3), indoleamine 2,3-dioxygenase 1 (IDO1), phosphatase and tensin homolog (PTEN), p53, AT-rich interactive domain-containing protein 1A (ARID1A), and β-catenin was performed using tissue microarray blocks.
Results: Among 123 patients, 95 (77.2%) were classified as having MSS. Within EC with MSS, PD-L1 positivity was significantly associated with positive PD-1 (p<0.001), CTLA-4 (p<0.001), CD3 (p=0.002), CD8 (p<0.001), and LAG-3 (p<0.001). In the univariate analysis, positive PD-1 (odds ratio [OR]=9.281; 95% confidence interval [CI]=2.560?33.653; p<0.001), CTLA-4 (OR=5.33; 95% CI=1.418?19.307; p=0.005), CD3 (OR=5.571; 95% CI=1.746?17.775; p=0.004), CD8 (OR=6.909; 95% CI=2.647?18.037; p<0.001), and LAG-3 (OR=9.75; 95% CI=1.947?48.828; p=0.005) were significantly associated with PD-L1 positivity in MSS EC. In the multivariate analysis, LAG-3 demonstrated a significant association with positive PD-L1 expression in MSS EC (OR=5.061; 95% CI=1.534?16.693; p=0.023).
Conclusion: In patients with MSS EC harboring PD-L1, LAG-3 may be a potential immunotherapeutic target. Clinical trials investigating the role of anti-LAG-3 antibodies, alone or in combination with other immunotherapies, are warranted.
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KEYWORD
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Lymphocyte Activation Gene-3, Programmed Cell Death-Ligand 1, Microsatellite Stable, Endometrial Neoplasms
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