Adjustment of dendritic cells to the breast-cancer microenvironment is subset specific

Nature Immunology
Paula MicheaVassili Soumelis

Abstract

The functions and transcriptional profiles of dendritic cells (DCs) result from the interplay between ontogeny and tissue imprinting. How tumors shape human DCs is unknown. Here we used RNA-based next-generation sequencing to systematically analyze the transcriptomes of plasmacytoid pre-DCs (pDCs), cell populations enriched for type 1 conventional DCs (cDC1s), type 2 conventional DCs (cDC2s), CD14+ DCs and monocytes-macrophages from human primary luminal breast cancer (LBC) and triple-negative breast cancer (TNBC). By comparing tumor tissue with non-invaded tissue from the same patient, we found that 85% of the genes upregulated in DCs in LBC were specific to each DC subset. However, all DC subsets in TNBC commonly showed enrichment for the interferon pathway, but those in LBC did not. Finally, we defined transcriptional signatures specific for tumor DC subsets with a prognostic effect on their respective breast-cancer subtype. We conclude that the adjustment of DCs to the tumor microenvironment is subset specific and can be used to predict disease outcome. Our work also provides a resource for the identification of potential targets and biomarkers that might improve antitumor therapies.

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Datasets Mentioned

BETA
PRJNA380940

Methods Mentioned

BETA
flow cytometry
RNA-seq
flow-cytometry

Software Mentioned

Tophat2
count
InterPro
EdgeR R
ARACNe
CytoScape
MonoMac
ClueGO Application
RUVSeq R
BubbleGUM

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