Research ArticleTUMOR IMMUNOLOGY

NF-κB–dependent IRF1 activation programs cDC1 dendritic cells to drive antitumor immunity

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Science Immunology  09 Jul 2021:
Vol. 6, Issue 61, eabg3570
DOI: 10.1126/sciimmunol.abg3570

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Unleashing tumor cDC1

Conventional type 1 dendritic cells (cDC1s) perform specialized roles in antitumor immunity by processing and presenting tumor antigens that prime tumor-specific T cell responses. Using a mouse model of immunogenic tumor growth and single-cell transcriptomics, Ghislat et al. demonstrate that cDC1s require NF-κB signaling for their intratumoral maturation into antitumoral cDC1s capable of recruiting and activating tumor-specific T cells. IKKβ controlled the expression of IRF1, a transcription factor regulating interferon-mediated gene expression, and loss of either factor in cDC1 impaired their maturation and antitumoral immunity. These results highlight key molecular pathways involved in the development of full-fledged cDC1 capable of stimulating antitumoral T cell responses and suggest potential therapeutic targets for improving intratumoral DC function.

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