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Omics · study · 2026

A20 stabilizes IRF8: De novo trogocytic cDC2s orchestrate robust anti-tumor immunity in cDC1-deficient A20cKO mice

Listed in NCBI GEO

Our study explored the role of the ubiquitin-editing enzyme A20 (TNFAIP3) in regulating conventional dendritic cell (cDC) differentiation and its implications for anti-tumor immunity.

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We found that A20 stabilizes IRF8, essential for type 1 cDC (cDC1) development, by removing K48-linked polyubiquitin chain. DC-specific A20-depleted (A20cKO) mice showed a significant reduction in cDC1 levels but exhibited robust anti-tumor immunity due to superior MHC-I-mediated antigen presentation by de novo type 2 cDCs (cDC2s).

These de novo cDC2s showed distinct gene expression profiles compared to wild-type cDC2s and acquired the ability to trogocytose adjacent tumor cells. NF-κB-dependent TNFα and TBK1/IRF3-mediated type I interferon secreted by cDCs in A20cKO mice played crucial roles in cDC2’s acquisition of cross-dressing characteristics, facilitating tumor-specific cytotoxic T lymphocyte responses even when cross-dressed with allo-tumor cells.

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This study highlights the crucial role of A20 in the development of cDC1s through IRF8 stabilization and unveils the unique anti-tumor potential of A20cKO cDC2s through their cross-dressing capabilities.

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Life Sciences
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Cancer 65%
Provenance · 1 source records, 8 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE31538814 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 (65%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-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