Journal
SCIENCE IMMUNOLOGY
Volume 5, Issue 46, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciimmunol.aav3942
Keywords
-
Categories
Funding
- INSERM
- INCA [PLBIO INCa_4508, PLBIO INCa_11155]
- ANRS
- ARC
- Ligue contre le Cancer (Regionale Auvergne-Rhone-Alpes et Saone-et-Loire, Comite de la Savoie)
- SiRIC LYriCAN [INCa-DGOS-Inserm_1263]
- Auvergne-Rhone-Alpes region (IRICE)
- Auvergne-Rhone-Alpes region
- ARC Foundation
- SIRIC project (LYRIC) [INCa_4664]
- FP7 European TumAdoR project [602200]
- LABEX DEVweCAN of the University of Lyon, within the program Investissements d'Avenir [ANR-10-LABX-0061]
Ask authors/readers for more resources
Dendritic cells play a key role in the orchestration of antitumor immune responses. The cDC1 (conventional dendritic cell 1) subset has been shown to be essential for antitumor responses and response to immunotherapy, but its precise role in humans is largely unexplored. Using a multidisciplinary approach, we demonstrate that human cDC1 play an important role in the antitumor immune response through their capacity to produce type III interferon (IFN-lambda). By analyzing a large cohort of breast primary tumors and public transcriptomic datasets, we observed specific production of IFN-lambda 1 by cDC1. In addition, both IFN-lambda 1 and its receptor were associated with favorable patient outcomes. We show that IFN-III promotes a T(H)1 microenvironment through increased production of IL-12p70, IFN-gamma, and cytotoxic lymphocyte-recruiting chemokines. Last, we showed that engagement of TLR3 is a therapeutic strategy to induce IFN-III production by tumor-associated cDC1. These data provide insight into potential IFN- or cDC1-targeting antitumor therapies.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available