a novel mechanism of tumor-induced thymic atrophy in mice bearing h22 hepatocellular carcinoma

Sujun Sun,* Haiyu Ji,* Yingying Feng, Yu Kang, Juan Yu, Anjun Liu Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin, China *These authors contributed equally to this work 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 (Tα1) 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. Keywords: thymic atrophy, T cells subsets, over-differentiation, H22 tumor