{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328683/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328683"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Programmable synthetic cytokine receptors polarize macrophages to user-defined functional states","description":"Macrophage-based immunotherapies hold promise for cancer and other diseases, but lack of methods to precisely control macrophage polarization limits both mechanistic understanding and therapeutic applications. Here, we use a programmable synthetic cytokine receptor (SCR) platform to control primary human macrophage polarization. SCRs containing signaling motifs from the interferon-gamma (IFN-γ) or Interleukin-10 (IL-10) receptors are sufficient to mimic pro-inflammatory or anti-inflammatory polarization, respectively. Combinatorial assembly of nine distinct signaling motifs within the SCR signaling domain generates a diverse landscape of synthetic macrophage states with varied expression of inflammatory markers (CD80, CD40, PDL1), anti-inflammatory markers (CD163, CD206) and phagocytic capacity. SCRs programmed with multiple YxxQ motifs drive macrophage phagocytosis of E. coli and chimeric antigen receptor (CAR)-macrophage phagocytosis of cancer cells in mice, reducing tumor burden by 30-fold. Quantitative analysis reveals that motif-dependent polarization follows a two-state equilibrium model, enabling rational prediction of macrophage polarization state from SCR composition. Leveraging this framework, we design SCRs that simultaneously enhance phagocytosis and maintain pro-inflammatory function. Together, these findings establish a framework to synthetically program macrophage polarization states with potential applications in cancer immunotherapy and other disease contexts.","dates":{"publication":"2026/08/05"},"accession":"GSE328683","cross_references":{"GSM":["GSM9687160","GSM9687161","GSM9687162","GSM9687151","GSM9687163","GSM9687152","GSM9687164","GSM9687153","GSM9687165","GSM9687154","GSM9687166","GSM9687155","GSM9687167","GSM9687156","GSM9687157","GSM9687168","GSM9687158","GSM9687159"],"GPL":["34284"],"GSE":["328683"],"taxon":["Homo sapiens"],"PMID":["[42182394]"]}}