TY - JOUR
T1 - Cutting edge
T2 - Hypoxia-induced nanog favors the intratumoral infiltration of regulatory T cells and macrophages via direct regulation of TGF-β1
AU - Hasmim, Meriem
AU - Noman, Muhammad Zaeem
AU - Messai, Yosra
AU - Bordereaux, Didier
AU - Gros, Gwendoline
AU - Baud, Veronique
AU - Chouaib, Salem
PY - 2013/12/15
Y1 - 2013/12/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84890378536&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1302140
DO - 10.4049/jimmunol.1302140
M3 - Article
AN - SCOPUS:84890378536
SN - 0022-1767
VL - 191
SP - 5802
EP - 5806
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -