Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells.
Inadequate presentation of tumor antigens by host professional antigen-presenting cells (APCs), including dendritic cells (DCs), is one potential mechanism for the escape of tumors from the host immune system. Here, we show that human cancer cell lines release a soluble factor or factors that dramatically affect DC maturation from precursors without affecting the function of relatively mature DCs. One factor responsible for these effects was identified as vascular endothelial growth factor (VEGF). Thus, VEGF may play a broader role in the pathogenesis of cancer than was previously thought, and therapeutic blockade of VEGF action may improve prospects for immunotherapy as well as inhibit tumor neovasculature.
Gabrilovich
D I
DI
Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas 75325, USA.
Chen
H L
HL
Girgis
K R
KR
Cunningham
H T
HT
Meny
G M
GM
Nadaf
S
S
Kavanaugh
D
D
Carbone
D P
DP
D017951:Antigen Presentation / Q000187:drug effects; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D016228:Endothelial Growth Factors / Q000494:pharmacology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D008222:Lymphokines / Q000494:pharmacology / Q000502:physiology*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000494:pharmacology / Q000502:physiology*; D009369:Neoplasms / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D017978:Receptors, Growth Factor / Q000032:analysis; D040262:Receptors, Vascular Endothelial Growth Factor; D011994:Recombinant Proteins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors; D016298:Hematopoietic Cell Growth Factors; D008222:Lymphokines; D009363:Neoplasm Proteins; D017978:Receptors, Growth Factor; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor