Association between cellular immune response and spleen weight in mice with hepatocellular carcinoma

Abstract

The spleen is an important site for extramedullary hematopoiesis and tumor immunotolerance. Spleen weight varies with tumor progression and may be a predictor of tumor recurrence. However, to the best of our knowledge, the association between spleen weight and tumor progression remains unclear. The present study revealed a novel role for the spleen in predicting the cellular immune response in tumor-bearing mice. A murine H22 subcutaneous hepatoma model was established. The spleen weight and tumor weight were measured. The proportion of immune cells in peripheral blood and spleen were detected by flow cytometry. The results demonstrated that the spleen weight of tumor-bearing mice at day 21 was higher than that of the controls. In addition, spleen weight was identified to be positively correlated with tumor weight. The percentages of CD4+ and CD8+ T lymphocytes in the spleen were decreased at day 21 after tumor cell inoculation, while those of monocytic-like myeloid-derived suppressor cells (M-MDSCs) and CD11b+F4/80+ macrophages were increased at day 21 after tumor cell inoculation. Similarly, the percentage of polymorphonuclear-like MDSCs (PMN-MDSCs) in the spleen of tumor-bearing mice was increased at days 7, 14 and 21 after tumor cell inoculation. Notably, spleen weight was negatively correlated with the percentages of CD4+ and CD8+ T lymphocytes in the spleen, although spleen and tumor weight were positively correlated with the percentages of M-MDSCs and PMN-MDSCs in the spleen. Similarly, the percentages of CD8+ T lymphocytes in the peripheral blood were decreased, and programmed cell death protein 1 expression on CD8+ T lymphocytes was increased at day 21 after tumor cell inoculation. Furthermore, the percentages of M-MDSCs were increased at day 21 and PMN-MDSCs in the peripheral blood were increased at days 7, 14 and 21 after tumor cell inoculation. Additionally, spleen and tumor weight were also positively correlated with the percentages of M-MDSC and PMN-MDSCs in the peripheral blood of tumor-bearing mice. Collectively, the findings of the present study suggested that spleen weight may be a predictor of tumor prognosis, since it was directly correlated with tumor weight and the percentages of M-MDSC and PMN-MDSCs in tumor-bearing mice.