Cutting edge: Hypoxia-induced nanog favors the intratumoral infiltration of regulatory T cells and macrophages via direct regulation of TGF-β1

Meriem Hasmim, Muhammad Zaeem Noman, Yosra Messai, Didier Bordereaux, Gwendoline Gros, Veronique Baud, Salem Chouaib*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

80 Citations (Scopus)

Abstract

Emerging evidence suggests a link between tumor hypoxia and immune suppression. In this study, we investigated the role of hypoxia-induced Nanog, a stemness-associated transcription factor, in immune suppression. We observed that hypoxia-induced Nanog correlated with the acquisition of stem cell-like properties in B16-F10 cells. We further show that Nanog was selectively induced in hypoxic areas of B16-F10 tumors. Stable short hairpin RNA-mediated depletion of Nanog, combined with melanocyte differentiation Ag tyrosinase-related protein-2 peptide-based vaccination, resulted in complete inhibition of B16-F10 tumor growth. Nanog targeting significantly reduced immunosuppressive cells (regulatory T cells and macrophages) and increased CD8+ T effector cells in tumor bed in part by modulating TGF-β1 production. Additionally, Nanog regulated TGF-β1 under hypoxia by directly binding the TGF-β1 proximal promoter. Collectively, our data establish a novel functional link between hypoxia-induced Nanog and TGF-β1 regulation and point to a major role of Nanog in hypoxia-driven immunosuppression.

Original languageEnglish
Pages (from-to)5802-5806
Number of pages5
JournalJournal of Immunology
Volume191
Issue number12
DOIs
Publication statusPublished - 15 Dec 2013
Externally publishedYes

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