Murine neuroblastoma attenuates dendritic cell cysteine cysteine receptor 7 (CCR7) expression.
OBJECTIVE
Dendritic cell (DC) migration from tumors to T-cell priming sites is critical in developing antitumor cytotoxicity. Cysteine cysteine receptor 7 (CCR7), a promigratory chemokine receptor, regulates DC recruitment to secondary lymphoid organs. Tumors may inhibit CCR7 expression to evade immunodetection. Previous work implicates impaired DC migration as a critical defect in immunity to neuroblastoma (NB). However, the mechanism has yet to be defined. We hypothesize that NB abrogates DC CCR7 expression and signaling, leading to decreased antitumor immunity.


METHODS
A/J mice (N = 36) were injected with saline (control) or murine NB (TBJ) and bone marrow-derived DC were isolated at 7, 14, and 28 days. CCR7 expression was analyzed by polymerase chain reaction, Western blot, and flow cytometry. Cytometry data were analyzed using the paired Student's t test.


RESULTS
Dendritic cells isolated from mice with NB had a 60% increase in CCR7 protein expression by flow cytometry compared with control mice at day 7. However, there was a 43% downregulation of CCR7 expression by DC from tumor-bearing mice compared with controls 2 weeks postinoculation (P < .005). These observations were confirmed by polymerase chain reaction and Western blot analysis.


CONCLUSIONS
Neuroblastoma initially upregulates CCR7 expression by DC. However, with tumor progression, this chemokine is downregulated, likely leading to impaired DC migration. Immunotherapeutic strategies to bypass or augment CCR7-dependent DC trafficking may improve survival for patients with aggressive disease.
Division of Pediatric Surgery, Children's Hospital of Pittsburgh, Pittsburgh, PA 15213-2583, USA.
Sonya R
SR
Walker
Alexander
A
Aboka
P Dafé
PD
Ogagan
Edward M
EM
Barksdale
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D003713:Dendritic Cells / Q000378:metabolism* / Q000502:physiology; D005786:Gene Expression Regulation; D051379:Mice; D008805:Mice, Inbred A; D009447:Neuroblastoma / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism*
C515371:Ccr7 protein, mouse; D012333:RNA, Messenger; D054400:Receptors, CCR7; D019707:Receptors, Chemokine