{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE325nnn/GSE325457/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325457"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Progesterone reshapes the tumor immune microenvironment towards macrophage-driven immune suppression in hormone receptor-positive breast cancer","description":"Hormone receptor–positive (HR⁺) breast cancers comprise ~80% of breast cancer cases, yet endocrine resistance remains a clinical barrier. While estrogen receptor alpha (ER) biology is well characterized, the role of progesterone receptor (PR) signaling in tumor progression and immune evasion is less defined. Using the ER⁺/PR⁺ SSM2 murine mammary tumor model, we investigated progesterone’s influence on tumor growth and the immune microenvironment. Progesterone significantly accelerated tumor growth in vivo and enhanced proliferation in vitro. Single-cell RNA sequencing (scRNA-seq) revealed that progesterone treatment reshaped the tumor microenvironment, expanding the tumor cell compartment while markedly reducing immune populations. Tumor-intrinsic analyses showed downregulation of interferon and antigen presentation pathways, alongside upregulation of cell cycle and proliferation signaling. Within the immune compartment, progesterone reduced overall T cell infiltration, shifted CD4⁺ T cells toward a regulatory phenotype, and increased macrophages. Notably, lipid-associated macrophages (LAMs) with a high Apoe/Trem2 signature were markedly expanded and engaged in immunosuppressive Spp1–CD44 signaling with immune cells. CellChat analysis of inferred ligand–receptor interactions revealed LAM-driven communication networks that may impair the anti-tumor immune response. Analysis of human breast cancer scRNA-seq datasets confirmed that PRhi tumors harbored more LAMs than PRlo tumors, supporting the translational relevance of our findings. Collectively, these data establish progesterone signaling as a driver of immune suppression in HR⁺ breast cancer through coordinated effects on tumor cells, T cells, and macrophages. Targeting PR signaling or LAM subsets may represent novel therapeutic strategies to overcome immune evasion and sensitize HR⁺ tumors to immunotherapy.","dates":{"publication":"2026/05/30"},"accession":"GSE325457","cross_references":{"GSM":["GSM9604185","GSM9604186","GSM9604183","GSM9604184","GSM9604182"],"GPL":["34328"],"GSE":["325457"],"taxon":["Mus musculus"]}}