NK and CD4 cells collaborate to protect against melanoma tumor formation in the brain.
NK cells represent a potent immune effector cell type that have the ability to recognize and lyse tumors. However, the existence and function of NK cells in the traditionally "immune-privileged" CNS is controversial. Furthermore, the cellular interactions involved in NK cell anti-CNS tumor immunity are even less well understood. We administered non-Ag-loaded, immature dendritic cells (DC) to CD8alpha knockout (KO) mice and studied their anti-CNS tumor immune responses. DC administration induced dramatic antitumor immune protection in CD8alpha KO mice that were challenged with B16 melanoma both s.c. and in the brain. The CNS antitumor immunity was dependent on both CD4+ T cells and NK cells. Administration of non-Ag-loaded, immature DC resulted in significant CD4+ T cell and NK cell expansion in the draining lymph nodes at 6 days postvaccination, which persisted for 2 wk. Finally, DC administration in CD8alpha KO mice was associated with robust infiltration of CD4+ T cells and NK cells into the brain tumor parenchyma. These results represent the first demonstration of a potent innate antitumor immune response against CNS tumors in the absence of toxicity. Thus, non-Ag-loaded, immature DC administration, in the setting of CD8 genetically deficient mice, can induce dramatic antitumor immune responses within the CNS that surpass the effects observed in wild-type mice. Our results suggest that a better understanding of the cross-talk between DC and innate immune cells may provide improved methods to vaccinate patients with tumors located both systemically and within the CNS.
Prins
Robert M
RM
Department of Surgery, Division of Neurosurgery, Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California-Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA. rprins@mednet.ucla.edu
Vo
Dan D
DD
Khan-Farooqi
Haumith
H
Yang
Meng-Yin
MY
Soto
Horacio
H
Economou
James S
JS
Liau
Linda M
LM
Ribas
Antoni
A
D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D016827:CD8 Antigens; D002450:Cell Communication / Q000276:immunology*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000637:transplantation; D007109:Immunity; D007694:Killer Cells, Natural / Q000276:immunology* / Q000502:physiology; D008198:Lymph Nodes / Q000166:cytology; D008546:Melanoma, Experimental / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain