NK cells are required for dendritic cell-based immunotherapy at the time of tumor challenge.
Increasing evidence suggests that NK cells act to promote effective T cell-based antitumor responses. Using the B16-OVA melanoma model and an optimized Gram-positive bacteria-dendritic cell (DC) vaccination strategy, we determined that in vivo depletion of NK cells at time of tumor challenge abolished the benefit of DC immunotherapy. The contribution of NK cells to DC immunotherapy was dependent on tumor Ag presentation by DC, suggesting that NK cells act as helper cells to prime or reactivate tumor-specific T cells. The absence of NK cells at tumor challenge resulted in greater attenuation of tumor immunity than observed with selective depletion of either CD4 or CD8 T cell subsets. Although successful DC immunotherapy required IFN-γ, perforin expression was dispensable. Closer examination of the role of NK cells as helper cells in enhancing antitumor responses will reveal new strategies for clinical interventions using DC-based immunotherapy.
Department of Microbiology and Immunology, Otago School of Medical Sciences, University of Otago, Dunedin 9001, New Zealand.
Anthea L
AL
Bouwer
Sarah C
SC
Saunderson
Felicity J
FJ
Caldwell
Tanvi T
TT
Damani
Simon J
SJ
Pelham
Amy C
AC
Dunn
Ralph W
RW
Jack
Patrizia
P
Stoitzner
Alexander D
AD
McLellan
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D019496:Cancer Vaccines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology / Q000637:transplantation*; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics / Q000276:immunology; D014611:Vaccination
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D052899:Pore Forming Cytotoxic Proteins; C483886:perforin, mouse; D007371:Interferon-gamma