Antigen presentation potential is variable among human ovarian tumour and syngeneic murine models and dictates pre-clinical outcomes of immunotherapy
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View abstract on PubMed
Summary
This summary is machine-generated.High grade serous ovarian carcinoma (HGSC) immunotherapy response depends on antigen presentation machinery (APM). MHC-I expression predicts treatment success, guiding better preclinical models and patient stratification for ovarian cancer.
Area Of Science
- Oncology
- Immunology
- Genetics
Background
- High grade serous ovarian carcinoma (HGSC) presents limited therapeutic options, with immunotherapy showing promise.
- Effective immunotherapy relies on MHC-I-dependent antigen presentation, but the antigen presentation machinery (APM) in HGSC models is poorly understood.
- This limits the translational relevance of preclinical studies for HGSC.
Purpose Of The Study
- To systematically evaluate APM gene expression in syngeneic murine HGSC models and patient tumors.
- To identify critical APM markers and correlate murine models with patient subsets.
- To assess the efficacy of a novel combination immunotherapy in HGSC models with varying APM status.
Main Methods
- Systematic evaluation of APM gene expression in murine HGSC models and patient samples.
- Identification of Tap1 and Psmb8 as critical APM markers.
- Hierarchical clustering correlation analysis to align murine models with patient subsets.
- In vivo testing of a combination immunotherapy (Flt3L, Poly(I:C), paclitaxel).
Main Results
- Tap1 and Psmb8 were identified as key APM markers, often deficient in murine models, correlating with MHC-I expression.
- ID8-p53⁻/⁻BRCA1⁻/⁻ and ID8-ip1 models showed strong correlation with distinct patient subsets.
- The combination immunotherapy significantly reduced tumor burden in high APM models (ID8-p53⁻/⁻BRCA1⁻/⁻, ID8-ip1) but not in the low MHC-I IG10 model.
- High MHC-I expression correlated with enhanced immune cell activity, including DC expansion, CD8⁺ T-cell infiltration, and activation.
Conclusions
- MHC-I serves as a predictive biomarker for immunotherapy response in HGSC.
- APM-enhancing strategies are crucial for improving immunotherapy in antigen-poor HGSC tumors.
- This study provides a framework for optimizing preclinical immunotherapy evaluation and patient stratification in HGSC.
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