Vaccination with Dendritic Cells Inhibits the Growth of Hepatic Metastases in B6 Mice

Dendritic cells (DC) are specialized antigen-presenting cells that can activate naive and mature T-cells, induce cellular immunity, and stimulate strong antitumor reactions in vivo. This study was undertaken to examine the function of DC vaccines in suppressing the growth of hepatic metastases in C57BL/6 mice. Experimental mice received two i.v. doses of 1 x 10(6) bone marrow-derived DC, either unpulsed or pulsed with MCA-106 fibrosarcoma cell lysates, on days -14 and -7. Controls were injected with HBSS. Hepatic metastases were established on day 0 through intrasplenic injections of 1 x 10(5) MCA-106 tumor cells. Animals were sacrificed on day 21 and their livers were excised to assess tumor burden. Splenocytes from DC-treated groups were cytotoxic against MCA-106 cells, but not against the L929 and CT26 (syngeneic fibroblast and colon tumor, respectively) cell lines. All control mice developed grossly evident hepatic metastases, while 62 and 44% of the mice receiving MCA-106 cell lysate-pulsed DC and unpulsed DC vaccines, respectively, were completely free of tumor. Mean hepatic mass for the controls, including tumor, was almost double that for treated animals. Antibody depletion of either CD4+ or CD8+ lymphocytes abrogated the protective effect of the vaccine. This study demonstrates that immunization with DC confers cellular immunity, with both CD4+ and CD8+ T-cells playing a significant role, and impedes the subsequent establishment and growth of hepatic metastases in mice. The antitumor capabilities of DC justify their use in immunotherapeutic vaccines against human cancers.