Dynamics of the spleen and its significance in a murine H22 orthotopic hepatoma model

Abstract

The dynamics of the spleen during tumor progression remains incompletely understood. In this study, we established a murine H22 orthotopic hepatoma model and dynamically detected alterations in the percentages of immunocytes in the spleen. We observed a prominent myeloid-derived suppressor cell (MDSC) accumulation during the early response which persisted through all the stages of tumor growth. In addition, the percentage of regulatory T cells (Tregs) increased by week 2. Although the percentage of CD3⁺CD49b⁺ natural killer T (NKT) cells increased by day 3, and that of CD3⁺CD4⁺ T cells slightly increased by week 1, they decreased to either normal or lower levels compared with those of normal mice. The percentages of total CD3⁺, CD3⁺CD4⁺, and CD3⁺CD8⁺ T cells decreased by week 2, and that of NK cells decreased by week 3. The activation of non-Treg CD4⁺ T cells was scarce. Moreover, splenic MDSCs of tumor-bearing mice suppressed the activation of splenocytes. Therefore, a negative immune response gradually prevailed over a positive immune response during tumor growth. In addition, splenectomy was performed at the time of tumor inoculation, and we found that splenectomy could prolong the survival time, reduce the tumor weights, decrease the ascites volumes, and ameliorate the immune status of the tumor-bearing mice. Splenectomy also decreased the percentage of MDSCs and increased the percentages of CD8⁺ T cells, NK, and NKT cells in tumor tissues. Additionally, splenectomy decreased the percentage of MDSCs and increased that of CD8⁺ T cells in peripheral blood. Overall, our findings suggest that immune-negative cells are dominant in the spleen during tumor progression. Splenectomy could be helpful to improve the immune responses of tumor-bearing hosts.