The Tumor Burden and Immune Dynamic Changes in Pancreatic Cancer Liver Metastasis

Abstract

Background: The prognosis of the patient with pancreatic cancer liver metastasis is very poor. Investigating the dynamic changes of pancreatic cancer (PC) liver metastasis may contribute to alleviate PC liver metastasis progression. Methods: Murine pa ncreatic cancer cell line Panc02 was transfected with GFP protein as tumor marker. 3×106 Panc02GPF+/mouse were injected into spleen to establish PC liver metastasis animal model. In 1 hour and Day1, 5, 10, 20, 35 after the operation, four mice were sacrificed and their liver were embedded into paraffin. Immunohistochemistry were uesd to evaluate the tumor burden and infiltrating CD8+T cell. Results: In 1 hour after operation, the tumor cells evenly distributed in liver. The tumor burden of liver metastasis slightly increased in Day5-10 and the distribution of the metastasis became clumped. In Day20, no metastasis was found in some mice but some had large patchy metastasis in their liver. In Day35, some had “normal” liver and some had nodular metastasis in the liver. No obvious characteristic distribution of CD8+T cell was found in 1hour and Day1 group. In Day5 CD8+T cells distributed in the edge of the metastasis. In Day10, CD8+T cells reached the peak and infiltrated in the center of metastasis. In Day20 and Day35 groups, those who had nodular liver metastasis obviously had lower CD8+T cell infiltration. Conclusions: Single pancreatic cancer cell successfully developing into nodular liver metastasis is the result of cancer cell and host interaction. Intervening the tumor microenvironment in early stage of metastasis may help reduce PC liver metastasis.