Cellular senescence contributes to tumor growth mediated by regulatory T cells in B-cell Non-Hodgkin's Lymphoma

Abstract Background B-cell non-Hodgkin's lymphoma (B-NHL) is a common malignant tumor of the lymphoid immune system. The pathogenic factors are not clear. In recent years, studies have shown that cellular senescence promotes tumor cell immune escape and leads to tumor progression, but how cellular senescence affects B-NHL has not been determined. Methods There were 12 patients in this study, including 6 cases of B-NHL and 6 cases of reactive lymph node hyperplasia. Senescence-associated β-galactosidase (SA-β-GAL) staining kit was used for aging staining. Regulatory T cells (Tregs) were detected by flow cytometry. The secreted cytokines were detected by enzyme-linked immunosorbent assay kit. Next, we induced the Human diffuse large B-cell lymphoma cell line (LY8) aging model with different concentrations of Tert-butyl hydroperoxide(tBHP) in vitro, and then cultured with normal human monocytes to detect cellular senescence, Tregs and cytokines. Results Compared with patients with reactive lymph node hyperplasia, the proportion of senescent cells in patients with B-NHL was significantly increased, accompanied by an increase in Tregs and a variety of pro-inflammatory and immunosuppressive cytokines. The aging model of LY8 was induced by different concentrations of tBHP in vitro and co-cultured with normal monocytes. We found that the aging phenomenon was the most obvious in the experimental group with different concentrations of 30μmol/L tBHP, and the levels of related cytokines and Tregs were significantly increased. Conclusion Cellular senescence and Tregs crosstalk each other, forming a complex tumor microenvironment and promoting the occurrence and development of lymphoma.