A novel mechanism of tumor-induced thymic atrophy in mice bearing H22 hepatocellular carcinoma

作者：Sun, Sujun; Ji, Haiyu; Feng, Yingying; Kang, Yu; Yu, Juan; Liu, Anjun^*

来源：Cancer Management and Research, 2018, 10: 417-424.

DOI：10.2147/CMAR.S157512

• thymic atrophy
• T cells subsets
• over-differentiation
• H22 tumor

Background: Thymic atrophy was discovered in tumor-bearing mice in recent years.
Methods: Flow cytometry was carried out including Annexin V-FITC/PI double staining, PI staining, Terminal dUTP nick-end labeling, CD3-FITC/CD19-PE and CD8-FITC/CD4-PE double staining. Enzyme-linked immunosorbent assay and polymerase chain reaction were also investigated.
Results: According to our experiments, we demonstrated that no signs of apoptosis in thymocytes were found in H22-bearing mice, while the proportions of CD4(+) T cells and CD8(+) T cells in thymuses were remarkably increased, the opposite tendency was found in peripheral bloods, and only CD3(+)CD8(+)T cells were discovered in H22 solid tumors. We further discovered that the level of thymosin alpha 1 (T alpha 1) and the expression of Wnt4 in thymus of H22-bearing mice were significantly improved than control, which indicated the active proliferation and differentiation of thymocytes. Our study revealed that CD8(+) T cells could not effectively eliminate H22 cells independently when CD4(+) T cells were suppressed by tumors, while the body would only enhance the differentiation and maturation of T cells in thymuses and release them to solid tumor to reinforce antitumor immunocompetence, leading to a vicious cycle which finally led to thymic atrophy.
Conclusion: Our data propose a novel mechanism of tumor-induced thymic atrophy regulated by abnormal immunoreaction and may provide new ideas for the immunotherapy of tumors.

• 出版日期2018
• 单位天津科技大学