Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells.
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.
Zou
W
W
Tulane Medical School, Section of Hematology and Medical Oncology, New Orleans, Louisiana, USA. wzou@tulane.edu
Machelon
V
V
Coulomb-L'Hermin
A
A
Borvak
J
J
Nome
F
F
Isaeva
T
T
Wei
S
S
Krzysiek
R
R
Durand-Gasselin
I
I
Gordon
A
A
Pustilnik
T
T
Curiel
D T
DT
Galanaud
P
P
Capron
F
F
Emilie
D
D
Curiel
T J
TJ
D017209:Apoptosis; D002277:Carcinoma / Q000098:blood supply / Q000276:immunology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology; D008213:Lymphocyte Activation; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000276:immunology*; D017469:Receptors, Fibronectin / Q000096:biosynthesis; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*; D013601:T-Lymphocytes / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D017469:Receptors, Fibronectin; D019010:Vascular Cell Adhesion Molecule-1; D016753:Interleukin-10