Intratumoral injection of dendritic cells after treatment of anticancer drugs induces tumor-specific antitumor effect in vivo.
We investigated the in vivo antitumor effects of intratumoral (i.t.) administration of dendritic cells (DC) after low-dose chemotherapy using cisplatin + 5-FU. Combination of i.t. injection of DC and systemic chemotherapy induced complete rejection of the treated tumor, MC38 murine adenocarcinoma. Furthermore, the antitumor effects were also observed on a distant tumor inoculated in the contralateral flank of the animal. When 10x the number of tumor cells were inoculated, the antitumor effect of the combination of DC after chemotherapy was also confirmed and in comparison to that of DC or chemotherapy alone, thereafter contributed to a greater prolongation of survival. To analyze the mechanisms of the systemic antitumor effect generated in this system, we assessed the cytolytic activity against inoculated tumors. The cytolytic activity of effector cells from treated animals was shown to be tumor-specific and was mainly CD8 and MHC Class-I (p < 0.01) restricted. CD4 and MHC Class-II treatment marginally inhibited the cytolytic activity but not significantly (p = 0.07, 0.08 respectively). The cytolysis of effector cells was enhanced more significantly by the treatment of both DC and chemotherapy, than that of either DC or chemotherapy alone. Our study suggests that the strategy of i.t. injection of DC after low-dose chemotherapy could be a powerful weapon to treat patients with cancer in the clinical settings.
Tanaka
Fumiaki
F
Division of Molecular and Surgical Oncology, Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
Yamaguchi
Hiroshi
H
Ohta
Mitsuhiko
M
Mashino
Kohjiro
K
Sonoda
Hideto
H
Sadanaga
Noriaki
N
Inoue
Hiroshi
H
Mori
Masaki
M
D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D002945:Cisplatin / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D007167:Immunotherapy; D015552:Injections, Intralesional; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
D002945:Cisplatin; D005472:Fluorouracil