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

Abstract

BackgroundThymic atrophy was discovered in tumor-bearing mice in recent years.MethodsFlow 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.ResultsAccording 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.ConclusionOur data propose a novel mechanism of tumor-induced thymic atrophy regulated by abnormal immunoreaction and may provide new ideas for the immunotherapy of tumors.

Influenza A virus‐induced thymus atrophy differentially affects dynamics of conventional and regulatory T‐cell development in mice

“…It remains to be defined whether the transiently altered Treg cell/Tconv ratio has an effect on the peripheral homeostasis of these cells, especially when the cause of this atrophy is more protracted or more frequently taking place. Since thymus atrophy has been reported to occur in the context of chronic infections [8] and cancer [52,53], it would be interesting to investigate the longlasting consequences of thymus atrophy on Treg cell homeostasis and function in those settings.…”

Influenza A virus-induced thymus atrophy differentially affects dynamics of conventional and regulatory T cell development

“…It remains to be defined whether the transiently altered Treg cell/Tconv ratio has an effect on the peripheral homeostasis of these cells, especially when the cause of this atrophy is more protracted or more frequently taking place. Since thymus atrophy has been reported to occur in the context of chronic infections [8] and cancer [51,52], it would be interesting to investigate the long-lasting consequences of thymus atrophy on Treg cell homeostasis and function in those settings.…”

Structural Characterization and Antitumor Activity of Polysaccharides from Kaempferia galanga L.

“…CD4 + T cells can modulate antitumor immune response in antitumor immunity via activating CD8 + T cells and NK cells; CD8 + T cells impart cytolytic activity on tumor cells [46]. NK cells belong to the innate lymphoid cell family and participate in damaging infected and cancerous cells [47].…”