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Updated: Aug 6, 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
Multiplexed Imaging Mass Cytometry Reveals Tumor-immune Microenvironment-dependent Hormone Receptor Expression in
Eleonora Y Khlebus1, Veena K Vuttaradhi1, Sammy Ferri-Borgogno1
1Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Abstract:
Adult-type granulosa cell tumors (AGCT) are rare ovarian tumors with few effective treatments for recurrent disease. To elucidate spatial features and cellular interactions within the AGCT tumor microenvironment, we applied imaging mass cytometry using a 34-marker panel on 130 regions from 24 AGCT samples, profiling more than 900,000 single cells. Analysis confirmed the immune "cold" phenotype of AGCTs and showed higher macrophage abundance in recurrent compared with primary tumors. We observed substantial heterogeneity in tissue architecture across samples, including variable presence of FOXL2+ cells embedded in collagen-rich regions (FOXL2+COL1A1+ cells). Based on tumor microenvironment composition, we defined two AGCT subtypes: AGCT-1 and AGCT-2 with distinct FOXL2+ cell distributions, differences in progesterone receptor expression, and unique transcriptomic profiles. Our findings highlight the role of macrophages, Foxl2+ subpopulations, and the extracellular matrix in AGCT progression and suggest AGCT subtype-specific vulnerabilities that could inform personalized therapies for this rare malignancy.
Significance:
We discovered two histologically and molecularly distinct forms of AGCTs that differ in cell composition, immune activity, and hormone signals. These findings point to new opportunities for more personalized treatment of this rare ovarian cancer.
Insights
Researchers identified two distinct subtypes of adult-type granulosa cell tumors (AGCTs) based on their microenvironment. This discovery offers new avenues for personalized treatment strategies for this rare ovarian cancer.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Adult-type granulosa cell tumors (AGCTs) are rare ovarian cancers with limited treatment options for recurrent disease.
- Understanding the tumor microenvironment is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the spatial features and cellular interactions within the AGCT tumor microenvironment.
- To identify distinct subtypes of AGCT based on microenvironment composition.
Main Methods:
- Imaging mass cytometry was used to analyze 130 regions from 24 AGCT samples, profiling over 900,000 single cells with a 34-marker panel.
- Analysis focused on immune cell infiltration, extracellular matrix components, and specific cell populations like FOXL2+ cells.
Main Results:
- AGCTs exhibit an immune "cold" phenotype, with increased macrophage abundance in recurrent tumors.
- Two distinct AGCT subtypes (AGCT-1 and AGCT-2) were identified, characterized by differences in FOXL2+ cell distribution, progesterone receptor expression, and transcriptomic profiles.
- Tumor heterogeneity was observed, including variable presence of FOXL2+ cells within collagen-rich areas.
Conclusions:
- The study highlights the roles of macrophages, FOXL2+ subpopulations, and the extracellular matrix in AGCT progression.
- The identified AGCT subtypes present distinct vulnerabilities, suggesting potential for subtype-specific, personalized therapeutic approaches for this rare malignancy.
