Type I IFN signaling on dendritic cells is required for NK cell-mediated anti-tumor immunity.
NK cells play a vital role in innate anti-tumor immunity. Crosstalk between NK cells and dendritic cells (DCs) has come to the forefront in protection against tumors in the context of DC vaccines. We previously discovered that NK cell activation mediates the anti-tumor activity elicited by DC vaccines in response to melanoma tumor challenge in a murine lung metastasis model. In this study, we sought to explore the mechanism behind this NK-DC communication, specifically looking at the involvement of IL-15 and type I IFN signaling. Using DCs from IL-15(-/-) and IL-15Rα(-/-) mice, we found that the anti-tumor effect of the vaccine remained comparable with DCs from wild type mice. Moreover, DCs derived from IFN-α/βR(-/-) mice also maintained their anti-tumor effect. Interestingly, endogenous DCs were found to accumulate in the draining lymph nodes post-immunization and their depletion abolished the anti-tumor effect of the vaccine. Our findings suggest the important role that type I IFN signaling and endogenous DCs play in DC vaccine-mediated anti-tumor protection. Our data suggest that type I IFNs from vaccine DCs activate host DCs to provide NK cell-mediated anti-tumor immunity.
Institute of Experimental Immunology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Khalil
K
Karimi
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.
Yalda
Y
Karimi
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.
Jeffrey
J
Chan
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.
Jeanette E
JE
Boudreau
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.
Jennifer
J
Basset
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.
Marianne V
MV
Chew
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.
Sarah
S
Reid
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.
Jonathan L
JL
Bramson
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.
Yonghong
Y
Wan
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada ashkara@mcmaster.ca.
Ali A
AA
Ashkar
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology; D002450:Cell Communication / Q000235:genetics; D003713:Dendritic Cells / Q000502:physiology* / Q000637:transplantation; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000378:metabolism; D016898:Interferon-alpha / Q000235:genetics; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000502:physiology*; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009362:Neoplasm Metastasis; D053647:Receptors, Interleukin-15 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*
D019496:Cancer Vaccines; D007370:Interferon Type I; D016898:Interferon-alpha; D019409:Interleukin-15; D053647:Receptors, Interleukin-15; C076799:interferon-alpha 8
DC vaccine; IL-15; IL-15Ra; NK cells; Type I interferon