Effective treatment of small murine hepatocellular carcinoma by dendritic cells
ABSTRACT
Hepatocellular carcinoma (HCC) is a common malignancy with a poor prognosis. This investigation examined whether dendritic cell-based immunotherapy can treat murine HCC effectively. Bone marrow-derived dendritic cells were propagated from C57BL/10J mice in GM-CSF (4 ng/mL) and interleukin (IL)-4 (1,000 micro/mL). The dendritic cells were pulsed with a Hepa1-6 lysate overnight and employed to treat murine HCC. For in vivo study, HCC was created by inoculation of hepa1-6, 5 x 10(5) cells, in the flank of C57BL/10J mice. HCC were categorized into small (3 x 3-mm) and large (5 x 5-mm) tumors. These HCC were treated by dendritic cells intravenously, twice at weekly intervals. The results revealed that lymphocytes could be gathered around small HCC after administration of Hepa1-6 lysate-pulsed dendritic cells. Seven of 12 (58.3%) small HCC could be eradicated completely by dendritic cell-based immunotherapy, and 33.3% of the small tumors responded to immunotherapy partially which were held in a stable condition for 34.0 +/- 7.4 days before the tumors regrew. For large HCC, lymphocytes did not gather around the tumors, and the tumors cannot be eradicated effectively by dendritic cells. However, dendritic cell-based immunotherapy could slow down the growth rate of large tumors (116.2 +/- 91.4 mm(3) vs. 234.0 +/- 149.1 mm(3) of the control on day 7, P =.043; and 280.3 +/- 224.7 mm(3) vs. 870.0 +/- 418.9 mm(3) of the control on day 17, P <.001). Conclusively, dendritic cells pulsed with a Hepa1-6 lysate can be employed to treat small HCC in vivo effectively. However, the efficacy of dendritic cell-based immunotherapy decreases while tumors grow.