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Updated: Aug 22, 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
Profiling the immune landscape in mucinous ovarian carcinoma
Nicola S Meagher1, Phineas Hamilton2, Katy Milne2
1School of Clinical Medicine, UNSW Medicine and Health, University of NSW Sydney, Sydney, New South Wales, Australia; Adult Cancer Program, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, New South Wales, Australia; The Daffodil Centre, The University of Sydney, A Joint Venture with Cancer Council New South Wales, Australia.
Objective:
Mucinous ovarian carcinoma (MOC) is a rare histotype of ovarian cancer, with low response rates to standard chemotherapy, and very poor survival for patients diagnosed at advanced stage. There is a limited understanding of the MOC immune landscape, and consequently whether immune checkpoint inhibitors could be considered for a subset of patients.
Methods:
We performed multicolor immunohistochemistry (IHC) and immunofluorescence (IF) on tissue microarrays in a cohort of 126 MOC patients. Cell densities were calculated in the epithelial and stromal components for tumor-associated macrophages (CD68+/PD-L1+, CD68+/PD-L1-), T cells (CD3+/CD8-, CD3+/CD8+), putative T-regulatory cells (Tregs, FOXP3+), B cells (CD20+/CD79A+), plasma cells (CD20-/CD79a+), and PD-L1+ and PD-1+ cells, and compared these values with clinical factors. Univariate and multivariable Cox Proportional Hazards assessed overall survival. Unsupervised k-means clustering identified patient subsets with common patterns of immune cell infiltration.
Results:
Mean densities of PD1+ cells, PD-L1- macrophages, CD4+ and CD8+ T cells, and FOXP3+ Tregs were higher in the stroma compared to the epithelium. Tumors from advanced (Stage III/IV) MOC had greater epithelial infiltration of PD-L1- macrophages, and fewer PD-L1+ macrophages compared with Stage I/II cancers (p = 0.004 and p = 0.014 respectively). Patients with high epithelial density of FOXP3+ cells, CD8+/FOXP3+ cells, or PD-L1- macrophages, had poorer survival, and high epithelial CD79a + plasma cells conferred better survival, all upon univariate analysis only. Clustering showed that most MOC (86%) had an immune depleted (cold) phenotype, with only a small proportion (11/76,14%) considered immune inflamed (hot) based on T cell and PD-L1 infiltrates.
Conclusion:
In summary, MOCs are mostly immunogenically 'cold', suggesting they may have limited response to current immunotherapies.
Insights
Mucinous ovarian carcinoma (MOC) is typically immunologically "cold," with limited T cell and PD-L1 infiltration. This suggests MOC may not respond well to current immune checkpoint inhibitor therapies.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Mucinous ovarian carcinoma (MOC) is a rare ovarian cancer subtype with poor outcomes.
- Limited understanding exists regarding the MOC immune microenvironment and potential response to immunotherapy.
Purpose of the Study:
- To investigate the immune landscape of MOC.
- To correlate immune cell infiltration patterns with clinical factors and patient survival.
- To identify patient subsets based on immune cell infiltration.
Main Methods:
- Multicolor immunohistochemistry and immunofluorescence on 126 MOC patient samples.
- Quantification of immune cell densities (macrophages, T cells, Tregs, B cells, plasma cells) in epithelial and stromal compartments.
- Survival analysis and unsupervised clustering to define immune phenotypes.
Main Results:
- MOC tumors are predominantly "cold" (86%), with low T cell and PD-L1 infiltration.
- Advanced stage MOC shows altered macrophage infiltration compared to early stage.
- Specific immune cell densities (e.g., FOXP3+ Tregs, PD-L1- macrophages) correlate with poorer survival, while plasma cells correlate with better survival.
Conclusions:
- MOC exhibits an immunologically "cold" phenotype.
- The findings suggest limited efficacy of current immunotherapies for most MOC patients.
- Further research may identify specific MOC subsets that could benefit from immunotherapy.
