Dendritic cells (DC) are key cellular players in the induction of antigen-specific anti-tumoral immunity. BDCA3high DC are equivalent to mouse CD8α+ DC and specialized for Ag cross-presentation. Interestingly, they are also the main producers of interferon-λ (IFN-λ), a recently discovered cytokine family with antiviral, anti-proliferative and anti-tumoral properties. In this study, we first demonstrated by multiparametric flow cytometry that human BDCA3high DC are present in breast and ovarian tumors. Secondly, we observed that their IFN-λ synthesis upon TLR3 activation is reduced compared to their blood equivalents. Using in vitro BDCA3high DC generated from CD34+ hematopoietic stem cells, we are currently deciphering mechanisms of this alteration. This study shows for the first time the infiltration of solid tumors by this rare DC subset and highlights a functional DC alteration which has to be taken into account in the design of new anti-tumoral immunotherapeutic strategies.

Grants: Ligue contre le cancer, ANRS, INCA (PL BIO2011-155)

Citation Format: Margaux Hubert, Anne-Claire Doffin, Estelle Verronese, Isabelle Durand, Christophe Caux, Jenny Valladeau-Guilemond. Human BDCA3high dendritic cells infiltrate breast and ovarian tumors but are functionally altered. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A61.