Intratumoral injection of dendritic cells after treatment of anticancer drugs induces tumor-specific antitumor effect in vivo

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We have investigated the in vivo antitumor effects of intratumoral(i.t.) administration of dendritic cells(DC) following low-dose chemotherapy using cisplatin plus 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 distanttumor inoculated in the contralateral flank of the animal. When the 10 times the number of tumor cells were inoculated, the antitumor effect of the combination of DC following 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 more significantly enhanced by the treatment of both DC and chemotherapy, than that of either DC or chemotherapy alone. This study suggests that the strategy of i.t.injection of DC following low-dose chemotherapy could be a powerful weapon to treat patients with cancer in the clinical settings.