Host absence of CCR5 potentiates dendritic cell vaccination.
Previous work has shown that dendritic cells (DCs) express specific chemokine receptors that allow for coordinated movement in vivo. To test the in vivo relevance of this, we used a murine melanoma system and knockout mice to investigate the function of the chemokine receptor CCR5 and its ligands, CCR ligand (CCL)3 and CCL5. We found that the lack of CCR5 in the host mouse resulted in delayed tumor growth, but this effect was overcome at a higher tumor load. With the administration of tumor charged DCs, CCR5(-/-) mice that had previously been injected with tumor were completely protected from tumor. This effect was dependent on the dose of tumor cells and the expression of CCR5 on the DC and its absence in the host. In contrast, the loss of the CCR5 ligand, CCL3, led to an early delay in tumor growth that did not persist, while the absence of the CCR5 ligand, CCL5, had no effect. Blocking the activity of CCR5 in the host may represent a new strategy for enhancing the activity of a therapeutic melanoma DC vaccine.
Ng-Cashin
Judith
J
Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Kuhns
Jennifer J
JJ
Burkett
Susan E
SE
Powderly
John D
JD
Craven
Robin R
RR
van Deventer
Hank W
HW
Kirby
Suzanne L
SL
Serody
Jonathan S
JS
D000276:Adjuvants, Immunologic / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D016026:Bone Marrow Transplantation; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000637:transplantation*; D007279:Injections, Subcutaneous; D008024:Ligands; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054397:Receptors, CCR3; D019713:Receptors, CCR5 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; C515351:Ccr3 protein, mouse; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D008024:Ligands; D019402:Macrophage Inflammatory Proteins; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019707:Receptors, Chemokine