Antitumor immunity induced by dendritic cell-based vaccination is dependent on interferon-gamma and interleukin-12.
BACKGROUND
This study was conducted to determine whether dendritic cells (DCs) pulsed with a tumor cell lysate can effectively vaccinate against tumor cells and to establish which cytokines are necessary.


METHODS
Each wild-type mouse received two subcutaneous immunizations (days 14 and 7) with either saline, tumor lysate, DCs, or tumor-lysate-pulsed DCs. Gamma-interferon (gamma-IFN), knock-out (KO), and interleukin-12 (IL-12) KO mice were also used in immunizations. A tumor challenge was given at day 0. Splenocytes were assayed for gamma-IFN production.


RESULTS
All saline-injected mice (n = 19) and all mice injected with tumor lysate (n = 9) developed tumors. Six of nine mice immunized with DCs alone and 6/24 mice treated with lysate-pulsed DCs developed a tumor. Splenocytes from both the saline- and lysate-immunized groups produced undetectable levels of gamma-IFN, while those from mice immunized with either DCs or pulsed DCs produced high levels of gamma-IFN. Four of five gamma-IFN KO mice developed tumors after immunization with tumor-lysate-pulsed DCs. None of four IL-12 KO mice developed a tumor after immunization with wild-type pulsed DCs and 1/10 wild-type mice developed tumor after immunization with IL-12 KO pulsed DCs. Three of four IL-12 KO mice developed tumors after immunization with IL-12 KO pulsed DCs.


CONCLUSIONS
Tumor-lysate-pulsed DCs can initiate an effective antitumor immune response. The presence of gamma-IFN in the host is essential for antitumor protection. In contrast, tumor protection is observed if IL-12 is present in either the host or the DCs.
Hiramoto
Jade S
JS
Department of Surgery, University of California, San Francisco, California 94143-0780, USA. HiroseR@surgery.ucsf.edu
Tsung
Kangla
K
Bedolli
Melanie
M
Norton
Jeffrey A
JA
Hirose
Ryutaro
R
D000818:Animals; D000917:Antibody Formation; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology*; D005434:Flow Cytometry; D007109:Immunity; D007371:Interferon-gamma / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D014611:Vaccination
D018664:Interleukin-12; D007371:Interferon-gamma