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Updated: Aug 10, 2026
An Orthotopic Model of Serous Ovarian Cancer in Immunocompetent Mice for in vivo Tumor Imaging and Monitoring of Tumor Immune Responses
Published on: November 28, 2010
Loss of Major Histocompatibility Complex Class I, CD8 + Tumor-infiltrating Lymphocytes, and PD-L1 Expression in
Shih-Yao Lin1,2, Jen-Fan Hang1,2,3, Chiung-Ru Lai1,3
1Departments of Pathology and Laboratory Medicine.
Abstract:
Ovarian clear cell carcinoma (OCCC), a chemoresistant ovarian cancer, shows a modest response to anti-programmed death-1/programmed death ligand-1 (PD-1/PD-L1) therapies. The effects of anti-PD-1/PD-L1 therapies rely on cytotoxic T-cell response, which is triggered by antigen presentation mediated by major histocompatibility complex (MHC) class I. The loss of MHC class I with simultaneous PD-L1 expression has been noted in several cancer types; however, these findings and their prognostic value have rarely been evaluated in OCCC. We collected data from 76 patients with OCCC for clinicopathologic analysis. Loss of MHC class I expression was seen in 44.7% of the cases including 39.3% to 47.4% of the PD-L1 + cases and was associated with fewer CD8 + tumor-infiltrating lymphocytes (TILs). PD-L1 positivity was associated with a higher number of CD8 + TILs. Cox proportional hazard models showed that high (≥50/mm 2 ) CD8 + TILs was associated with shorter disease-specific survival (hazard ratio [HR]=3.447, 95% confidence interval [CI]: 1.222-9.720, P =0.019) and overall survival (HR=3.053, 95% CI: 1.105-8.43, P =0.031). PD-L1 positivity using Combined Positive Score was associated with shorter progression-free survival (HR=3.246, 95% CI: 1.435-7.339, P =0.005), disease-specific survival (HR=4.124, 95% CI: 1.403-12.116, P =0.010), and overall survival (HR=4.489, 95% CI: 1.553-12.972, P =0.006). Loss of MHC class I may contribute to immune evasion and resistance to anti-PD-1/PD-L1 therapies in OCCC, and CD8 + TILs and PD-L1 positivity using Combined Positive Score may have a negative prognostic value.
Insights
Ovarian clear cell carcinoma (OCCC) with loss of MHC class I and PD-L1 expression shows reduced T-cell response. High CD8+ T-cells and PD-L1 positivity are linked to poorer survival outcomes in OCCC patients.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Ovarian clear cell carcinoma (OCCC) is chemoresistant and shows limited response to anti-programmed death-1/programmed death ligand-1 (PD-1/PD-L1) therapies.
- Anti-PD-1/PD-L1 efficacy depends on cytotoxic T-cells, which require antigen presentation via major histocompatibility complex (MHC) class I.
- Loss of MHC class I and PD-L1 expression is observed in cancers, but its role in OCCC is understudied.
Purpose of the Study:
- To investigate the association between MHC class I expression, PD-L1 positivity, CD8+ tumor-infiltrating lymphocytes (TILs), and clinical outcomes in OCCC.
- To evaluate the prognostic significance of MHC class I loss, PD-L1 expression, and CD8+ TILs in OCCC patients.
Main Methods:
- Clinicopathologic analysis of data from 76 OCCC patients.
- Assessment of MHC class I expression, PD-L1 expression (using Combined Positive Score), and CD8+ TILs.
- Cox proportional hazard models were used to determine prognostic values.
Main Results:
- Loss of MHC class I expression was found in 44.7% of OCCC cases and correlated with fewer CD8+ TILs.
- PD-L1 positivity was associated with a higher number of CD8+ TILs.
- High CD8+ TILs (≥50/mm²) and PD-L1 positivity were significantly associated with shorter disease-specific survival and overall survival. PD-L1 positivity also correlated with shorter progression-free survival.
Conclusions:
- Loss of MHC class I may contribute to immune evasion and resistance to anti-PD-1/PD-L1 therapies in OCCC.
- Elevated CD8+ TILs and PD-L1 positivity (using Combined Positive Score) may serve as negative prognostic markers in OCCC.
