Effect of splenectomy on antitumor immune system in mice.
BACKGROUND
The influence on the antitumor immune system after splenectomy in vivo are controversial. CD4+CD25+Foxp3+T-cells (regulatory T-cell: reg T) and natural killer (NK) cells play important roles in immunological tolerance and antitumor immunity. The influence of splenectomy on the antitumor immune system was evaluated in a metastasis induced mouse model.


METHODS
Experiment 1, splenectomy in a cancer-free model. The mice were divided into two groups, one control, and the other splenectomy group. At days 4, 7 and 10 after splenectomy, the mesenteric lymph node, the liver and the lung were harvested. The lymph nodes were analyzed by flow cytometric analysis and the number of reg T-cells and NK cells were calculated. Foxp3 mRNA in the liver and the lung was evaluated by reverse transcriptional polymerase chain reaction (RT-PCR). Experiment 2, splenectomy in a liver metastasis model. Colon 26 cells were injected into the spleen of mice and the mice were divided into two groups, a spleen preserved group, and a splenectomy group. Splenectomy was performed at day 4 after injection. At days 7 and 10 after injection, flow cytometric analysis, and at day 10 RT-PCR were performed. Ten days after injection, the number of liver metastases (>1 mm) was counted.


RESULTS
Experiment 1, in the splenectomy group the flow cytometric analysis showed a significant decrease in the number of reg T and NK cells in the mesenteric lymph nodes compared with the control group. In the splenectomy group, the Foxp3 mRNA increased significantly in the liver at day 10, and in the lung at days 4 and 7. Experiment 2, liver metastasis was observed in the splenectomy group. Flow cytometric analysis showed that splenectomy did not affect the number of reg T at day 7 and day 10. The number of NK cells increased in the splenctomy group at day 7, but at day 10, there was no significant difference between the groups. RT-PCR showed that at day 10, the Foxp3 mRNA in liver increased in the splenectomy group.


CONCLUSIONS
The spleen plays a very important role in the antitumor immune system and splenectomy enhances liver metastasis through the increase of Foxp3 mRNA in the liver.
Higashijima
Jun
J
Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
Shimada
Mitsuo
M
Chikakiyo
Motoya
M
Miyatani
Tomohiko
T
Yoshikawa
Kozo
K
Nishioka
Masanori
M
Iwata
Takashi
T
Kurita
Nobuhiro
N