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Excel · study · 2026

Tumor-Associated Senescent Non-Classical Monocytes Promote Immune Suppression and Progression of Advanced Prostate Cancer [CUT&Run]

Listed in NCBI GEO

Prostate cancer, a leading cause of male cancer mortality, poses major therapeutic hurdles due to its immunosuppressive tumor microenvironment (TME).

Description

We link MYC amplification and PTEN deletion to metastatic prostate adenocarcinoma and identify a specific population of tumor-associated non-classical monocytes (staNC-Mo, CD11b+Ly6cLowCD14HiCD43LowCX3CR1Low) as key mediators of immune suppression. MYC overexpression with Pten loss induces mitochondrial stress, triggering tumor-cell apoptosis and HSP60 release.

The HSP60/TLR4 signaling activates staNC-Mo to secrete TNF-α, stimulating endothelial G-CSF production and driving staNC-Mo differentiation in bone marrow and spleen. CD14-dependent phagocytosis of apoptotic tumor cells drives staNC-Mo senescence and TGF-β1 secretion. TGF-β1 activates PI3K/AKT signaling in tumor cells, inducing CXCL5 secretion and reinforcing staNC-Mo recrutiment.

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Senescent staNC-Mo also release IL-18, suppressing innate and adaptive immunity. Targeting Ly6c, CD14, CXCL5-CXCR2, TLR4, or IL-18 reduces staNC-Mo accumulation, relieves TME immunosuppression, and inhibits tumor progression, suggesting therapeutic strategies for advanced prostate cancer.

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Life Sciences
Inferred from text
Cancer 75%
Provenance · 1 source records, 8 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE34543913 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:cancerenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:genome-binding-occupancy-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[organism].NCBITaxon:10090source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title