(The) role of spleen for anti-tumor effect and tumor-infiltrating T lymphocytes in an orthotopic murine pancreatic cancer model

Abstract

Background: Splenectomy during cancer surgery might negatively influence on the oncologic outcomes of the patients. The purpose of this study is to investigate whether simultaneously splenectomy influences the tumor growth pattern in an orthotopic murine pancreatic cancer model. Materials and Methods: Murine pancreatic cancer cells (PAN02) were subcutaneously injected into the flank of nude mouse. A small tumor fragment (3 mm2), harvested from a subcutaneously injected nude mouse, was orthotopically implanted in the pancreas tail of C57/BL6 mouse without splenectomy (control group, n=15) or with simultaneous splenectomy (splenectomy group, n=15). Tumor growth patterns were analyzed by laparotomy at 21st day after surgery. Results: Tumor rejection was observed in one mouse of control group. No tumor growth was found in 5 mice (33.3%) of control group and 1 mouse (6.7%) of splenectomy group (p=0.169). Tumor width and total tumor volume were significantly larger in splenectomy group (p=0.017; p=0.013, respectively). Peritoneal seeding was more frequently identified in the splenectomy group (11 (73.3%) vs. 4 (26.7%), p=0.011). There were no differences in the number of liver and kidney metastasis between the two groups. The ratios of tumor-infiltrating CD4+ to FoxP3+ and CD8+ to FoxP3+ were significantly higher in the control group compared to the splenectomy group (8.2 ± 9.3 vs. 2.4 ± 1.5, p=0.046; 2.5 ± 1.4 vs. 1.5 ± 0.4, p=0.031, respectively). Conclusion: Splenectomy enhanced tumor growth and peritoneal seeding in an orthotopic syngeneic murine pancreatic cancer mice model. The ramifications of these results are discussed for pancreatic cancer treatment.