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Updated: Dec 12, 2025
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
An Immunophenotyping of Ovarian Cancer With Clinical and Immunological Significance
Kai Yang1, Weiwei Zhao1, Ge Lou2
1Department of Epidemiology and Biostatistics, School of Public Health, Harbin Medical University, Harbin, China.
Abstract:
Immune checkpoint blockade (ICB), mainly anti-CTLA-4 and anti-PD-1/PD-L1 therapy, has showed promising clinical benefits in the treatment of some cancer types; however, its application in ovarian cancer is still in the primary stage. Immunophenotyping can help us understand the clinical characteristics and immune status of cancer, and thus benefit immunotherapy and personalized therapy. In this study, we clustered 907 ovarian cancer patients into three immune molecular subtypes (IMMSs) based on 48 genes. Expression data were downloaded from the Gene Expression Omnibus database. Unsupervised consensus clustering was used to identify IMMS. Clinical and immunological characteristics and gene expression patterns of different IMMS were compared, and associations between IMMS and tumor microenvironment immune types were explored. Three IMMSs with different clinical and immunological characteristics were identified, in which type I and II ovarian cancer patients were similar to each other. There were more serous and low-grade tumors in type I and II ovarian cancer. IMMS was associated with disease-free survival before and after adjusting for clinical characteristics and ICB-related genes. Among the differentially expressed genes identified in our study, about 90% (25/28) were highly expressed in type I and II ovarian cancer. Genes related to ICB (CTLA-4, PD-L1, and PD-L2) and cytotoxic lymphocytes (CD8A, GZMA, and PRF1) were all highly expressed in type I and II ovarian cancer. Patients with type I and II ovarian cancer may be more sensitive to anti-CTLA-4 therapy, anti-PD-1/PD-L1 therapy, and a combination of immunotherapies. In contrast, patients with type III ovarian cancer may be insensitive to these treatments and require new therapies.
Insights
Ovarian cancer patients were classified into three immune molecular subtypes (IMMSs). Types I and II ovarian cancers show higher immune checkpoint blockade (ICB) gene expression, suggesting better response to ICB therapies.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Immune checkpoint blockade (ICB) therapies, including anti-CTLA-4 and anti-PD-1/PD-L1, show promise in various cancers but are underutilized in ovarian cancer.
- Immunophenotyping aids in understanding cancer's immune status, crucial for advancing immunotherapy and personalized treatment strategies.
Purpose of the Study:
- To classify ovarian cancer patients into distinct immune molecular subtypes (IMMSs) using gene expression data.
- To investigate the clinical and immunological characteristics of each IMMS.
- To explore the association between IMMS and response to ICB therapies.
Main Methods:
- Unsupervised consensus clustering of gene expression data from 907 ovarian cancer patients.
- Analysis of 48 key genes to identify IMMS.
- Comparison of clinical features, immune profiles, and gene expression patterns across identified IMMS.
Main Results:
- Three distinct IMMSs were identified, with Type I and Type II exhibiting similar characteristics, including a higher prevalence of serous and low-grade tumors.
- IMMS classification was significantly associated with disease-free survival, independent of clinical factors and ICB-related genes.
- Genes associated with ICB (CTLA-4, PD-1, PD-L1, PD-L2) and cytotoxic lymphocytes (CD8A, GZMA, PRF1) were highly expressed in Type I and II IMMS.
- Type III IMMS showed distinct immunological profiles, suggesting potential resistance to current ICB therapies.
Conclusions:
- Ovarian cancer can be stratified into three IMMSs with differing clinical and immunological features.
- Type I and II ovarian cancers demonstrate an immune profile potentially predictive of sensitivity to anti-CTLA-4 and anti-PD-1/PD-L1 immunotherapies.
- Type III ovarian cancer patients may not benefit from current ICB treatments and require novel therapeutic approaches.
