Omics · study · 2026
Programmable synthetic cytokine receptors polarize macrophages to user-defined functional states
Listed in NCBI GEO
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.
Description
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.
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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.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328683 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328683 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1456125 ncbi.nlm.nih.gov/bioproject/PRJNA1456125 ↗
project · from NCBI GEO
- PubMed 42182394 pubmed.ncbi.nlm.nih.gov/42182394 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Biochemistry and cell biology 71% · Cancer 75% · Disease 75%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE328683 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].anzsrc:group:3101 | enrichment · NCBI GEO | taxonomy-embedding@1.1.0 | title+keywords+description (71%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |