PD-L1 and MHC Class I Expression in High-grade Ovarian Cancers, Including Platinum-resistant Recurrences Treated With...

Area of Science:

• Oncology
• Immunology
• Pathology

Background:

• Immune-modulating therapies targeting programmed cell death-1/programmed cell death ligand-1 (PD-L1) are effective in various solid tumors.
• Biomarkers such as PD-L1 and major histocompatibility complex (MHC) class I are explored for predicting response to checkpoint inhibition.
• Evidence for these biomarkers in ovarian malignancies remains limited.

Purpose of the Study:

• To evaluate the utility of PD-L1 and MHC class I as predictive biomarkers for immunotherapy response in high-grade ovarian carcinoma.
• To investigate the co-occurrence of PD-L1 expression and MHC class I loss as immune evasion mechanisms.

Main Methods:

• PD-L1 and MHC class I immunostaining on pretreatment tissue sections from 30 high-grade ovarian carcinoma cases.
• Calculation of PD-L1 combined positive score (CPS) and categorization of MHC class I status (intact or subclonal loss).
• Assessment of immunotherapy response using RECIST criteria in patients with platinum-resistant recurrence.

Main Results:

• PD-L1 positivity was observed in 87% of cases (CPS ≥ 1).
• Subclonal loss of MHC class I occurred in 23% of patients, including PD-L1 negative and positive cases.
• Only 1 of 17 patients with platinum-resistant recurrence responded to immunotherapy; all 17 died of disease, irrespective of biomarker status.

Conclusions:

• PD-L1 and MHC class I immunostains may not be effective predictive biomarkers in recurrent ovarian cancer.
• Subclonal MHC class I loss occurs in PD-L1 positive ovarian tumors, indicating potential for combined immune evasion.
• Interrogating MHC class I status in PD-L1 positive tumors is crucial for understanding multifaceted immune evasion.