The tumour microenvironment harbours ontogenically distinct dendritic cell populations with opposing effects on tumour immunity

Damya Laoui, Jiri Keirsse, Yannick Morias, Eva Van Overmeire, Xenia Geeraerts, Yvon Elkrim, Máté Kiss, Evangelia Bolli, Qods Lahmar, Dorine Sichien, Jens Serneels, Charlotte L Scott, Louis Boon, Patrick De Baetselier, Massimiliano Mazzone, Martin Guilliams, Jo A Van Ginderachter

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Various steady state and inflamed tissues have been shown to contain a heterogeneous DC population consisting of developmentally distinct subsets, including cDC1s, cDC2s and monocyte-derived DCs, displaying differential functional specializations. The identification of functionally distinct tumour-associated DC (TADC) subpopulations could prove essential for the understanding of basic TADC biology and for envisaging targeted immunotherapies. We demonstrate that multiple mouse tumours as well as human tumours harbour ontogenically discrete TADC subsets. Monocyte-derived TADCs are prominent in tumour antigen uptake, but lack strong T-cell stimulatory capacity due to NO-mediated immunosuppression. Pre-cDC-derived TADCs have lymph node migratory potential, whereby cDC1s efficiently activate CD8(+) T cells and cDC2s induce Th17 cells. Mice vaccinated with cDC2s displayed a reduced tumour growth accompanied by a reprogramming of pro-tumoural TAMs and a reduction of MDSCs, while cDC1 vaccination strongly induces anti-tumour CTLs. Our data might prove important for therapeutic interventions targeted at specific TADC subsets or their precursors.

Original languageEnglish
Pages (from-to)13720
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 23 Dec 2016

Fingerprint

Dive into the research topics of 'The tumour microenvironment harbours ontogenically distinct dendritic cell populations with opposing effects on tumour immunity'. Together they form a unique fingerprint.

Cite this