AsGM1+NK cells prevent metastasis of invading LD-MCA-38 tumor cells in thenude mouse

Background. Although the liver is a potent tumor cell killing organ it is f requently the site of lethal metastases often signifying the endstage for p atients with colorectal cancers. Enhancing hepatic-associated immunity rema ins elusive until the interactions among hepatic nonparenchymal cells (NPC) are deciphered. We sought to modulate the cellular components of the hepat ic immune system of mice with anti-NK and anti-T-cell-neutralizing antibodi es in order to determine the cell type most efficacious in preventing liver metastasis. Materials and methods. Liver-derived murine colon adenocarcinoma (LD-MCA-38 ) cells were injected into the ileocolic vein (ICV) of immunocompetent and immunodeficient C57BL/6 mice. Mice were pretreated 1 day prior to tumor cel l injection with one of three antibodies: anti-AsGM1, Anti-NK1.1, or Anti-T hy1.2. On Day 21 laparotomy was performed to determine the extent of hepati c tumor foci. The number of hepatic tumor foci was recorded and compared by the Wilcoxon rank sum test. Results. Mice pretreated with anti-AsGM1 or Anti-NK1.1 developed a massive increase in the number of hepatic tumor foci and decreased survival compare d to the control treated mice. Pretreatment with anti-Thy1.2 antibody resul ted in a significant decrease in the number of hepatic tumor foci, LD-MCA-3 8 tumor cells were unable to colonize the liver of C57BL/6 athymic nude mic e; however, anti-AsGM1 antibody abolished this antimetastatic effect. There was no difference in the extent of hepatic metastasis and survival between immunodeficient C57BL/6 bg/bg and their conventional littermates bg/+. Conclusion. AsGM1+ NK cells exhibit a significant antitumor response in the absence of T-cells. The concept of stimulating NK cell activity and suppre ssing T-cell function may enhance liver-associated immunity and serve as a deterrent for blood-borne tumor cells metastasizing to the liver. (C) 1999 Academic Press.