Effects of colorectal cancer liver metastases on intrahepatic B cells (P2093)

Abstract

Abstract Background: We and others have found that liver metastases (LM) mediate tolerogenic effects. B cells make up a significant proportion of liver lymphocytes but their function in the normal liver and in the setting of LM is poorly defined. Therefore, we attempted to define the features of HBC in the setting of LM. Methods: We have used a murine model of CEA+ colorectal LM to study the effects of malignancy on HBC. Tumor cells were injected into the portal circulation of C57Bl/6 mice to induce LM, and HBC were analyzed after two weeks. Results: 50% of mice with LM secreted anti-CEA antibodies, suggesting that the tumor is recognized by B cells in our model. HBC comprised 45±10% of lymphocytes in normal livers, and their frequency was reduced in mice with LM (25±3%, p=0.03). A significant reduction in the frequency of IgM+IgDlo transitional B cells, precursors of mature B cells, was observed in mice with LM (23±2% and 8±4% in normal and metastatic livers respectively, p=0.02). HBC exhibited significant down-regulation of two molecules associated with T cell activation: MHCII (7.5±3.5%, down from 31±5% in normal livers, p=0.03) and CD80 (0.9±0.4%, down from 9.6±1.4% in normal livers, p=0.02). Conclusion: The ability of HBC to mount an immune response may be compromised in the setting of LM as evidenced by reduction of HBC number and diminished HBC expression of MHCII and CD80. Further research is needed to elucidate the function of hepatic B cells during liver metastasis.