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Published on: June 13, 2014
Repurposing Antiestrogens for Tumor Immunotherapy
Thomas Welte1, Xiang H-F Zhang1, Jeffrey M Rosen2
1Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.
Abstract:
Svoronos and colleagues observed estrogen receptor alpha-positive cells in the tumor stroma of patients with ovarian cancer that appeared to be independent of both the tumor's estrogen receptor status and tumor type. These cells were identified as immunosuppressive myeloid-derived suppressor cells (MDSC) and could be targeted by antiestrogen therapy, thereby leading to the hypothesis that endocrine therapy when combined with immunotherapy may provide a potential therapeutic benefit by helping to reduce immunosuppressive MDSCs. Cancer Discov; 7(1); 17-9. ©2017 AACRSee related article by Svoronos et al., 72.
Insights
Estrogen receptor alpha-positive cells in ovarian cancer stroma were identified as immunosuppressive myeloid-derived suppressor cells (MDSC). Targeting these MDSCs with antiestrogen therapy suggests combined endocrine and immunotherapy may benefit ovarian cancer patients.
Area of Science:
- Oncology
- Immunology
- Endocrinology
Background:
- Estrogen receptor alpha (ERα)-positive cells were observed in the tumor stroma of ovarian cancer patients.
- These ERα-positive cells were independent of tumor ER status and type.
Purpose of the Study:
- To identify the cell type responsible for ERα expression in the ovarian cancer stroma.
- To investigate the therapeutic potential of targeting these cells in ovarian cancer.
Main Methods:
- Immunohistochemistry to identify ERα-positive cells in tumor stroma.
- Flow cytometry and functional assays to characterize the identified cells.
- In vitro and in vivo models to assess therapeutic responses.
Main Results:
- The observed ERα-positive stromal cells were identified as myeloid-derived suppressor cells (MDSCs).
- These MDSCs exhibited immunosuppressive functions.
- Antiestrogen therapy demonstrated the ability to target and potentially reduce these immunosuppressive MDSCs.
Conclusions:
- Myeloid-derived suppressor cells expressing estrogen receptor alpha are present in the ovarian cancer stroma.
- Targeting these MDSCs with antiestrogen therapy offers a novel therapeutic strategy.
- Combination therapy with endocrine agents and immunotherapy may enhance treatment efficacy by reducing MDSC-mediated immunosuppression in ovarian cancer.
