Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells

Weiping Zoul, Véronique Machelon, Aurore Coulomb-L’Hermin, Jozef Borvakz, FranÇoise Nome, Tatyana Isaeva, Shuang Wei, Roman Krzysieks, Ingrid Durand-Gasselin, Alan Gordon, Terri Pustilnik, David T. Curiel, Pierre Galanaud, Frédérique Capron, Dominique Emilie, Tyler J. Curiel

Research output: Contribution to journalArticlepeer-review

505 Scopus citations

Abstract

Dendritic-cell (DC) trafficking and function in tumors is poorly characterized, with studies confined to myeloid DCs (DC1s). Tumors inhibit DC1 migration and function, likely hindering specific immunity. The role of plasmacytoid Dcs (DC2s) in tumor immunity is unknown. We show here that malignant human ovarian epithelial tumor cells express very high levels of stromal-derived factor-1, which induces DC2 precursor (preDC2) chemotaxis and adhesion/transmigration, upregulates preDC2 very late antigen (VLA)-5, and protects preDC2s from tumor macrophage interleukin-10-induced apoptosis, all through CXC chemokine receptor-4. The VLA-5 ligand vascular-cell adhesion molecule-1 mediated preDC2 adhesion/transmigration. Tumor preDC2s induced significant T-cell interleukin-10 unrelated to preDC2 differentiation or activation state, and this contributed to poor T-cell activation. Myeloid precursor Dcs (preDC1s) were not detected. Tumors may weaken immunity by attracting preDC2s and protecting them from the harsh microenvironment, and by altering preDC1 distribution.

Original languageEnglish (US)
Pages (from-to)1339-1346
Number of pages8
JournalNature Medicine
Volume7
Issue number12
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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