Effect Of Cell Senescence On Tumor Microenvironment In B-cell Non-Hodgkin’s Lymphoma

Background and objective:Non-Hodgkin lymphoma(NHL)is a group of malignant tumors from the blood system.The World Health Organization divides NHL into more than 40 types based on pathological and histological characteristics,of which about85% are derived from B cells(B-cell Non-Hodgkin lymphoma(B-NHL)).Investigations have shown that the occurrence of B-NHL may be closely related to factors such as viral or bacterial infections,changes in the immune environment,and genetic mutations.The traditional treatment methods for lymphoma include radiotherapy and chemotherapy,bone marrow transplantation and so on.With the emergence of CD20 monoclonal antibodies,individualized therapy,and targeted cell therapy,the prognosis and survival of B-NHL have been further improved.However,the problem of refractory recurrence in invasive lymphoma still exists.Cell senescence refers to a relatively stable cell cycle arrest,triggered by a variety of factors including shortening of telomeres,activation of oncogenes,and DNA damage.Cell aging is a complex,multifactorial process that may have a wide range of effector mechanisms.At the molecular level,aging triggers important changes in gene expression patterns.On the other hand,senescent cells can secrete a variety of factors and proteases,called the Senescence-Associated Secretory Phenotype(SASP),and SASP can play a role with immune cells in the tumor microenvironment(TME)Effect,promote tumor immune escape,leading to refractory patients with relapse.The occurrence and development of lymphoma has a close relationship with TME.On the one hand,TME includes the structure,function and metabolism of the tissue in which the tumor is located;on the other hand,it is closely related to the internal environment of the tumor cells.Tumor cells can change and maintain their environment through autocrine and paracrine to promote their own development.The whole body and local tissues can also limit and influence tumor development through metabolism,secretion,and changes in structure and function.Therefore,studying the effect of TME on B-NHL from the perspective of cell aging has great clinical value for the treatment and prognosis of B-NHL.Methods:Collect peripheral blood and lymph node tissue samples from B-NHL patients,detect the expression of senescent cells in peripheral blood mononuclear cells of B-NHL patients;detect CD4 + T cells,NK cells,and regulatory T cells(Regulatory T Cells)in peripheral blood Tergs),Myeloid-derived suppressor cells(MDSCs)expression levels;detection of the expression of related cytokines in SASP in peripheral blood serum;observation of lymphoma cell morphology;detection of tumor-associated lymphoma tissue Tumor-associated macrophages(TAMs)expression levels.The experimental data obtained were analyzed and plotted using SPSS19.0 and Graph Prism6.Results:B-NHL patients had senescent cells in peripheral blood mononuclear cells,and the initial diagnosis group and the non-responding group were higher than those in the remission group.In the detection of CD4 + T cells,the expression level of the remission group was higher than that of the first diagnosis group and the non-remission group;in the detection of NK cells,the expression level of the remission group was higher than that of the non-remission group;in the detection of Tregs,the non-remission group The expression level was higher than that in the remission group.In M-MDSCs,the expression level in the newly diagnosed group was higher than in the remission group;in G-MDSCs,the expression levels in the remission group and the non-remission group were higher than in the first diagnosis group.In the detection of cytokines,Interleukin-2(IL-2),Interleukin-6(IL-6),Interleukin-8(IL-8),Vascular endothelial growth factor(VEGF)The expression level of the newly diagnosed cytokine group was higher than that of the remission group;in IL-8,the expression level of the non-responded group was higher than that of the first diagnosis group;in IL-6,interleukin-10(IL-10),transforming growth factor-β(Among cytokines such as Transforming growth factor-β(TGF-β)and Tumor necrosis factor-α(TNF-α),the expression level in the non-responding group was also higher than that in the remission group;in interleukin-35(IL-35),the expression level of the remission group showed a downward trend compared with the newly diagnosed group and the non-remission group.In the detection of TAMs,CDl63-positive products in lymphoma tissues were localized on the cell membrane of macrophages and stained yellow-brown or tan.Stained cells were rarely seen in reactive hyperplasia of lymph nodes,and CD163 was low expressed.Conclusion:Cell senescence exists in peripheral blood mononuclear cells in patients with B-NHL.Lymphoma cells,immune cells,and cytokines and inhibitors secreted by SASP participate in the formation of complex TME.In the early stage of lymphoma development,the effect of SASP on TME can promote the body to effectively kill lymphoma cells.As the disease progresses,TME has a reverse effect on SASP,and promotes lymphoma cells to escape the monitoring of the immune system and chemoradiation.At the end of the treatment,the senescent tumor cells can be revived and reproduced,which eventually leads to relapse and refractory treatment for lymphoma patients.