ArticleJCI insight2020
Ovarian granulosa cell tumor characterization identifies FOXL2 as an immunotherapeutic target.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Role of adjuvant chemotherapy in stage IC ovarian granulosa cell tumors: a systematic review and meta-analysis.Journal of gynecologic oncology · 2025Pooled it
- SWOG/NCI Phase II Dual Anti-CTLA-4/PD-1 Blockade in Rare Tumors: Nonepithelial Ovarian Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Article
- Visual analysis of ovarian cancer immunotherapy: a bibliometric analysis from 2010 to 2025.Frontiers in medicine · 2025Review
- Advanced Granulosa Cell Tumors of the Ovary: A Review with a Focus on Current and Novel Therapeutic Approaches.Journal of immunotherapy and precision oncology · 2024Review
- Metabolic characteristics of granulosa cell tumor: role of PPARγ signaling†.Biology of reproduction · 2024Article
- Clinical characteristics and oncological outcomes of recurrent adult granulosa cell tumor of ovary: A retrospective study of seventy patients.Acta obstetricia et gynecologica Scandinavica · 2023Article
- Comparative Tumor Microenvironment Analysis of Primary and Recurrent Ovarian Granulosa Cell Tumors.Molecular cancer research : MCR · 2023Article
- Mechanisms of primordial follicle activation and new pregnancy opportunity for premature ovarian failure patients.Frontiers in physiology · 2023Review
- Transcriptomic Profiling of Gene Expression Associated with Granulosa Cell Tumor Development in a Mouse Model.Cancers · 2022Article
- Highly efficient PD-1-targeted CRISPR-Cas9 for tumor-infiltrating lymphocyte-based adoptive T cell therapy.Molecular therapy oncolytics · 2022Article
- Combination of vasculature targeting, hypofractionated radiotherapy, and immune checkpoint inhibitor elicits potent antitumor immune response and blocks tumor progression.Journal for immunotherapy of cancer · 2021Article
- On Deep Landscape Exploration of COVID-19 Patients Cells and Severity Markers.Frontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Granulosa cell tumors (GCT) are rare ovarian malignancies. Due to the lack of effective treatment in late relapse, there is a clear unmet need for novel therapies. Forkhead Box L2 (FOXL2) is a protein mainly expressed in granulosa cells (GC) and therefore is a rational therapeutic target. Since we identified tumor infiltrating lymphocytes (TILs) as the main immune population within GCT, TILs from 11 GCT patients were expanded, and their phenotypes were interrogated to determine that T cells acquired late antigen-experienced phenotypes and lower levels of PD1 expression. Importantly, TILs maintained their functionality after ex vivo expansion as they vigorously reacted against autologous tumors (100% of patients) and against FOXL2 peptides (57.1% of patients). To validate the relevance of FOXL2 as a target for immune therapy, we developed a plasmid DNA vaccine (FoxL2-tetanus toxin; FoxL2-TT) by fusing Foxl2 cDNA with the immune-enhancing domain of TT. Mice immunization with FoxL2-TT controlled growth of FOXL2-expressing ovarian (BR5) and breast (4T1) cancers in a T cell-mediated manner. Combination of anti-PD-L1 with FoxL2-TT vaccination further reduced tumor progression and improved mouse survival without affecting the female reproductive system and pregnancy. Together, our results suggest that FOXL2 immune targeting can produce substantial long-term clinical benefits. Our study can serve as a foundation for trials testing immunotherapeutic approaches in patients with ovarian GCT.
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