Tumor Immunology Inhibition of spontaneous development of liver tumors by inoculation with dendritic cells loaded with hepatocellular carcinoma cells in C3H/HeNCRJ mice Masaki Irie 1 2, Sadamu Homma 1 2 *, Hideo Komita 1 2, Mikio Zeniya 1, Donald Kufe 3, Tsuneya Ohno 2, Gotaro Toda 1 1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan 2Department of Oncology, Institute of DNA Medicine, Jikei University School of Medicine, Tokyo, Japan 3Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA email: Sadamu Homma (sahya@jikei.ac.jp) *Correspondence to Sadamu Homma, Department of Oncology, Institute of DNA Medicine, Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, Japan 105-8461 Fax: +81-3-3435-0569 or +81-3-3433-1230 Abstract We attempted to prevent spontaneous development of liver tumors by s.c. inoculation with DCs loaded with syngeneic HCC cells in C3H/HeNCrj mice. A new cell line, MIH-2, was established from an HCC that had developed spontaneously in a C3H/HeNCrj mouse. Bone marrow-derived DCs were loaded with irradiated MIH-2 cells by treatment with PEG. Fluorescence microscopy and flow-cytometric analysis showed that about 45% of PEG-treated DCs and MIH-2 cells (DC/MIH-2) were DCs loaded with MIH-2 cells. Thirteen-month-old mice received inoculations of DC/MIH-2 (9 × 105/mouse) 4 times at 6-day intervals and were killed at 16 months of age to assess liver tumors. The incidence of liver tumors in these mice was significantly lower than that in mice not receiving inoculations (p < 0.05) but similar to that in 13-month-old mice (the age at which inoculation started), indicating that inoculation inhibited the development of new tumors. Splenocytes from inoculated mice, but not those from uninoculated mice, showed cytotoxic activity against MIH-2 cells. Cytotoxic activity was not elicited by CD4+ T cells, CD8+ T cells, or DX5+ cells isolated from splenocytes but was elicited by adherent cells, identified as CD11b+ macrophages. CD4+ T cells, but not CD8+ T cells, from inoculated mice produced IFN- by incubation with DC/MIH-2. Cytotoxicity by splenocytes was attenuated by anti-IFN- antibody. Immunization with DCs loaded with syngeneic HCC cells induces CD4+ T cells that produce IFN- by response to antigen of HCC, which would lead to macrophage activation to kill liver tumor cells at an early stage. International Journal of Cancer Volume 111, Issue 2 , Pages 238 - 245 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.