Dendritic cells coinjected with tumor cells treated with an anticancer drug to induce tumor rejection.
OBJECTIVE
We examined whether bone marrow-derived dendritic cells (DCs) could induce antitumor immunity when a chemotherapeutic drug was added.


METHODS
CT26 (a murine colon cancer cell line syngeneic with BALB/c) and CT26-bearing mice were treated with mitomycin C (MMC) intraperitoneally (i.p.). Next, mice immunized with a coinjection of DCs and MMC-treated CT26 (i.p.) were given an intradermal inoculation of CT26. Finally, CT26-bearing mice were treated with MMC (i.p.) with or without DCs, given peritumorally.


RESULTS
Although the inoculated tumor was not rejected in the control mice, CT26 was rejected in 50% of the mice injected with MMC alone. Apoptosis was observed in the MMC-treated CT26 cells in vitro and in vivo. Immunization with DCs and apoptotic CT26 cells, but not with apoptotic CT26 alone, gave protection against tumor challenge in 7 of 13 mice. A significantly higher level of cytotoxic T-cell activity and interferon-gamma production was seen in the protected mice. When MMC (i.p.) treatment was followed by peritumoral DC injection in the CT26-bearing mice, remarkable therapeutic effects were observed.


CONCLUSIONS
DCs can collaborate with chemotherapy-induced apoptotic tumor cells and elicit improved antitumor immunity, probably through the acquisition of tumor-associated antigens from apoptotic tumor cells.
Inoue
Naoya
N
Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, 54 Shogoin, Kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Yamasaki
Seiji
S
Kondo
Kan
K
Kan
Takatsugu
T
Furumoto
Katsuyoshi
K
Imamura
Masayuki
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D017209:Apoptosis / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D016685:Mitomycin / Q000627:therapeutic use*; D009369:Neoplasms / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000903:Antibiotics, Antineoplastic; D016685:Mitomycin