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| Status |
Public on Aug 16, 2021 |
| Title |
An NF-κB/IRF1 axis programs cDC1 to drive antitumor immunity II |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
functions of cDC1s are poorly understood. We mapped the molecular pathways regulating intratumoral cDC1 maturation using single cell RNA sequencing. We identified NF-κB and IFN pathways as being highly enriched in a subset of functionally mature cDC1s. The specific targeting of NF-κB or IFN pathways in cDC1s prevented the recruitment and activation of CD8+ T cells and the control of tumor growth. We identified an NF-κB-dependent IFN-γ-regulated gene network in cDC1s, including cytokines and chemokines specialized in the recruitment and activation of cytotoxic T cells. We used single cell transcriptomes to map the trajectory of intra-tumoral cDC1 maturation which revealed the dynamic reprogramming of tumor-infiltrating cDC1s by NF-κB and IFN signaling pathways. This maturation process was perturbed by specific inactivation of either NF-κB or IRF1 in cDC1s, resulting in impaired expression of IFN-γ-responsive genes and consequently a failure to efficiently recruit and activate anti-tumoral CD8+ T cells. Finally, we demonstrate the relevance of these findings to cancer patients, showing that activation of the NF-κB/IRF1 axis in association with cDC1s is linked with improved clinical outcome. The NF-κB/IRF1 axis in cDC1s may therefore represent an important focal point for the development new diagnostic and therapeutic approaches to improve cancer immunotherapy.
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| Overall design |
We performed bulk RNA-seq analysis of cDC1s sorted from YUMM1.7 tumors in female IkbkbF/F and IkbkbΔXcr1 mice.
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| Contributor(s) |
Ghislat G, Vu Manh T, Dalod M, Lawrence T |
| Citation(s) |
34244313 |
| |
| Submission date |
May 07, 2021 |
| Last update date |
Aug 16, 2021 |
| Contact name |
Thien-Phong Vu Manh |
| Organization name |
CIML
|
| Street address |
163 avenue de Luminy
|
| City |
marseille |
| ZIP/Postal code |
13288 |
| Country |
France |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA728126 |
| SRA |
SRP318936 |
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