Batf3 -Dependent Genes Control Tumor Rejection Induced by Dendritic Cells Independently of Cross-Presentation

The BATF3-dependent cDC1 lineage of conventional dendritic cells (cDC) is required for rejection of immunogenic sarcomas and for rejection of progressive sarcomas during checkpoint blockade therapy. One unique function of the cDC1 lineage is the efficient cross-presentation of tumor-derived neoantig...

Full description

Saved in:
Bibliographic Details
Published in:Cancer immunology research 2019-01, Vol.7 (1), p.29-39
Main Authors: Theisen, Derek J, Ferris, Stephen T, Briseño, Carlos G, Kretzer, Nicole, Iwata, Arifumi, Murphy, Kenneth M, Murphy, Theresa L
Format: Article
Language:English
Subjects:
Animals
Basic-Leucine Zipper Transcription Factors - genetics
Cell Line, Tumor
Dendritic Cells - immunology
Female
Fibrosarcoma - genetics
Fibrosarcoma - immunology
Graft Rejection - genetics
Graft Rejection - immunology
Interferon Regulatory Factors - genetics
Lymph Nodes - immunology
Male
Mice, Inbred C57BL
Mice, Knockout
Oligonucleotide Array Sequence Analysis
Repressor Proteins - genetics
Spleen - immunology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The BATF3-dependent cDC1 lineage of conventional dendritic cells (cDC) is required for rejection of immunogenic sarcomas and for rejection of progressive sarcomas during checkpoint blockade therapy. One unique function of the cDC1 lineage is the efficient cross-presentation of tumor-derived neoantigens to CD8 T cells, but it is not clear that this is the only unique function of cDC1 required for tumor rejection. We previously showed that BATF3 functions during cDC1 lineage commitment to maintain IRF8 expression in the specified cDC1 progenitor. However, since cDC1 progenitors do not develop into mature cDC1s in mice, it is still unclear whether BATF3 has additional functions in mature cDC1 cells. A transgenic -Venus reporter allele increases IRF8 protein concentration sufficiently to allow autonomous cDC1 development in spleens of mice. These restored cDC1s are transcriptionally similar to control wild-type cDC1s but have reduced expression of a restricted set of cDC1-specific genes. Restored cDC1s are able to cross-present cell-associated antigens both and However, cDC1 exhibit altered characteristics and are unable to mediate tumor rejection. These results show that BATF3, in addition to regulating expression to stabilize cDC1 lineage commitment, also controls expression of a small set of genes required for cDC1-mediated tumor rejection. These BATF3-regulated genes may be useful targets in immunotherapies aimed at promoting tumor rejection.
ISSN:2326-6066
2326-6074
DOI:10.1158/2326-6066.cir-18-0138