ArticleJournal for immunotherapy of cancer2021
Progesterone promotes immunomodulation and tumor development in the murine mammary gland.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- The immunology of human breast cancer.Nature reviews. Immunology · 2026Review
- Breast cancer immunogenicity as a spectrum: evolving concepts and therapeutic implications.The Journal of clinical investigation · 2026Review
- Sex Steroid Hormone Regulation of T-Cell Function and Antitumor Immunity.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- Preoperative onapristone-XR in postmenopausal women with progesterone receptor-positive (PgR+)/HER2-negative early breast cancer: SOLTI-1802 ONAWA trial results.NPJ breast cancer · 2026Article
- Sex Differences in Cancer Immunotherapy-Clinical Evidence and Mechanisms With a Focus on NSCLC.Immunological reviews · 2026Review
- Decoding the mechanisms underlying breast cancer brain metastasis: paving the way for precision therapeutics.Biomarker research · 2025Review
- Spatial profiling reveals unique immune microenvironment in premenopausal triple-negative breast cancer associated with therapy response.Journal of translational medicine · 2025Article
- Progesterone receptor-dependent downregulation of MHC class I promotes tumor immune evasion and growth in breast cancer.Journal for immunotherapy of cancer · 2025Article
- Site-specific O-GlcNAcylation of progesterone receptor (PR) supports PR attenuation of interferon stimulated genes (ISGs) and tumor growth in breast cancer.The Journal of biological chemistry · 2024Article
- Progesterone boosts abiraterone-driven target and NK cell therapies against glioblastoma.Journal of experimental & clinical cancer research : CR · 2024Article
- Senescence-associated secretory phenotype (SASP) and uterine fibroids: Association with PD-L1 activation and collagen deposition.Ageing research reviews · 2024Review
- Hallmarks of sex bias in immuno-oncology: mechanisms and therapeutic implications.Nature reviews. Cancer · 2024Article
- Estrogen Receptor Alpha Mutations, Truncations, Heterodimers, and Therapies.Endocrinology · 2024Review
- Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- The Great Immune Escape: Understanding the Divergent Immune Response in Breast Cancer Subtypes.Cancer discovery · 2023Review
- Tailoring therapies to counter the divergent immune landscapes of breast cancer.Frontiers in cell and developmental biology · 2023Review
- Role of gonadally synthesized steroid hormones in the colorectal cancer microenvironment.Frontiers in oncology · 2023Review
- Progesterone Receptor Modulates Extraembryonic Mesoderm and Cardiac Progenitor Specification during Mouse Gastrulation.International journal of molecular sciences · 2022Article
- Mechanosensitive Steroid Hormone Signaling and Cell Fate.Endocrinology · 2022Article
- Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor.Nature communications · 2022Article
Corrections and comments
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Authors and funding
23 authors at 7 institutions in 1 country.
Funding
Abstract
backgroundClinical studies have linked usage of progestins (synthetic progesterone [P4]) to breast cancer risk. However, little is understood regarding the role of native P4, signaling through the progesterone receptor (PR), in breast tumor formation. Recently, we reported a link between PR and immune signaling pathways, showing that P4/PR can repress type I interferon signaling pathways. Given these findings, we sought to investigate whether P4/PR drive immunomodulation in the mammary gland and promote tumor formation.
methodsTo determine the effect of P4 on immune cell populations in the murine mammary gland, mice were treated with P4 or placebo pellets for 21 days. Immune cell populations in the mammary gland, spleen, and inguinal lymph nodes were subsequently analyzed by flow cytometry. To assess the effect of PR overexpression on mammary gland tumor development as well as immune cell populations in the mammary gland, a transgenic mouse model was used in which PR was overexpressed throughout the entire mouse. Immune cell populations were assessed in the mammary glands, spleens, and inguinal lymph nodes of 6-month-old transgenic and control mice by flow cytometry. Transgenic mice were also monitored for mammary gland tumor development over a 2-year time span. Following development of mammary gland tumors, immune cell populations in the tumors and spleens of transgenic and control mice were analyzed by flow cytometry.
resultsWe found that mice treated with P4 exhibited changes in the mammary gland indicative of an inhibited immune response compared with placebo-treated mice. Furthermore, transgenic mice with PR overexpression demonstrated decreased numbers of immune cell populations in their mammary glands, lymph nodes, and spleens. On long-term monitoring, we determined that multiparous PR-overexpressing mice developed significantly more mammary gland tumors than control mice. Additionally, tumors from PR-overexpressing mice contained fewer infiltrating immune cells. Finally, RNA sequencing analysis of tumor samples revealed that immune-related gene signatures were lower in tumors from PR-overexpressing mice as compared with control mice.
conclusionTogether, these findings offer a novel mechanism of P4-driven mammary gland tumor development and provide rationale in investigating the usage of antiprogestin therapies to promote immune-mediated elimination of mammary gland tumors.
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