ArticleProceedings of the National Academy of Sciences of the United States of America2023
Steroid receptor coactivator 3 is a key modulator of regulatory T cell-mediated tumor evasion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- A Systematic Review of Immune Cell Roles in Breast Cancer Immunotherapy.Cancer reports (Hoboken, N.J.) · 2025Pooled it
- Steroid receptor coactivator 3-deficient regulatory T cells eradicate multiple solid tumors in syngeneic mouse models.Oncoimmunology · 2026Article
- LSD1 Promotes Immune Exclusion and Suppresses IFN-γ-Associated Transcriptional Programs in Triple-Negative Breast Cancer.Cancers · 2026Article
- Steroid receptor coactivators: from basic research to translational opportunities.Endocrine reviews · 2026Review
- Steroid receptor coactivators in immunity - From function to emerging translational opportunities.The Journal of biological chemistry · 2026Review
- Uncovering Mediating Mechanisms Linking Immune Cells to Systemic Lupus Erythematosus: Insights into Mendelian Randomization.Endocrine, metabolic & immune disorders drug targets · 2026Article
- Method for generation and ex vivo expansion of genetically edited mouse Tregs.Journal of leukocyte biology · 2025Article
- PFKFB4 promotes endometrial cancer by regulating glycolysis through SRC‑3 phosphorylation.Oncology reports · 2025Article
- A long journey to the discovery of nuclear receptor coactivator existence, physiology, pathology, and therapy.The Journal of biological chemistry · 2025Article
- Nanoparticles Modulating the Immune Microenvironment in Breast Cancer Treatment.International journal of nanomedicine · 2025Review
- Unraveling the breast cancer tumor microenvironment: crucial factors influencing natural killer cell function and therapeutic strategies.International journal of biological sciences · 2025Review
- Immune evasion and resistance in breast cancer.American journal of cancer research · 2025Review
- Modulation of the immune microenvironment using nanomaterials: a new strategy for tumor immunotherapy.Frontiers in immunology · 2025Review
- Immune Cell Migration to Cancer.Cells · 2024Review
- Androgen Receptor-Interacting Proteins in Prostate Cancer Development and Therapy Resistance.The American journal of pathology · 2024Review
- Selective targeting or reprogramming of intra-tumoral Tregs.Medical oncology (Northwood, London, England) · 2024Review
- Function of Steroid Receptor Coactivators in T Cells and Cancers: Implications for Cancer Immunotherapy.Critical reviews in immunology · 2024Review
- Steroid receptor coactivators in Treg and Th17 cell biology and function.Frontiers in immunology · 2024Review
- Antitumor immunostimulatory activity of the traditional Chinese medicine polysaccharide on hepatocellular carcinoma.Frontiers in immunology · 2024Review
- Critical Roles of SRC-3 in the Development and Progression of Breast Cancer, Rendering It a Prospective Clinical Target.Cancers · 2023Review
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Steroid receptor coactivator 3 (SRC-3) is most strongly expressed in regulatory T cells (Tregs) and B cells, suggesting that it plays an important role in the regulation of Treg function. Using an aggressive E0771 mouse breast cell line syngeneic immune-intact murine model, we observed that breast tumors were "permanently eradicated" in a genetically engineered tamoxifen-inducible Treg-cell-specific SRC-3 knockout (KO) female mouse that does not possess a systemic autoimmune pathological phenotype. A similar eradication of tumor was noted in a syngeneic model of prostate cancer. A subsequent injection of additional E0771 cancer cells into these mice showed continued resistance to tumor development without the need for tamoxifen induction to produce additional SRC-3 KO Tregs. SRC-3 KO Tregs were highly proliferative and preferentially infiltrated into breast tumors by activating the chemokine (C-C motif) ligand (Ccl) 19/Ccl21/chemokine (C-C motif) receptor (Ccr)7 signaling axis, generating antitumor immunity by enhancing the interferon-γ/C-X-C motif chemokine ligand (Cxcl) 9 signaling axis to facilitate the entrance and function of effector T cells and natural killer cells. SRC-3 KO Tregs also show a dominant effect by blocking the immune suppressive function of WT Tregs. Importantly, a single adoptive transfer of SRC-3 KO Tregs into wild-type E0771 tumor-bearing mice can completely abolish preestablished breast tumors by generating potent antitumor immunity with a durable effect that prevents tumor reoccurrence. Therefore, treatment with SRC-3-deleted Tregs represents an approach to completely block tumor growth and recurrence without the autoimmune side effects that typically accompany immune checkpoint modulators.
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