The Study Of Relationship Between Senescence-triggered Cell Senescence And B-cell Non-hodgkin's Lymphoma

Background and objective:Non-Hodgkin lymphoma?NHL?is a malignant tumor of the lymphoid immune system.It originates from lymph nodes and lymphoid tissues,of which B cells account for about 85%?B-NHL?..The pathogenic factors of B-NHL are still unclear.A large number of investigations have shown that physical and chemical factors,infection,immunity,and genetic factors are involved in the formation of lymphoma.In recent years,with the advent and application of rituximab,chimeric B cell antigen CD19 receptor T cells?CAR-T-CD19?and other targeted drugs,as well as the continuous improvement of chemotherapy and the comprehensive application of hematopoietic stem cell transplantation,the therapeutic effect of B-NHL has been significantly improved.Despite this,there are still some patients who die due to refractory or recurrent disease and uncontrollable conditions.The reasons may be that B-NHL has the characteristics of leukemia and other solid tumors,so its ability to escape immune destruction is more rigorous and complex.Therefore,we need to study the immune escape mechanism of B-NHL more thoroughly.Immune escape is the hallmark ability of malignant tumor cells,and cell senescence refers to a state in which cells are subjected to one or more kinds of pressure from inside and outside the environment,and the cells lose their proliferative ability and enter a state of continuous quiescence.It is generally believed that senescence is an important barrier to prevent tumor formation.However,with the deepening of research on cell aging,it is found that cell senescence does not permanently stop proliferation or progress toward apoptosis.In the process of cell senescence,the body repairs abnormal genes.Stabilization,as well as the body's various physical and chemical stimuli,may provide opportunities for senescent cells to produce new oncogenes or drug-resistant genes,leading to senescent cells to resurrect,and even become more value-added cancer cells.SENEX is a new cloned new gene related to senescence.This paper studies the causes and mechanisms of B-NHL tumor cell formation and immune escape from the perspective of SENEX gene triggering cell senescence,and provides new ideas and theoretical basis for the treatment of B-NHL.Methods:The lymph nodes and peripheral blood of patients with B-NHL?6 cases?and reactive lymph node hyperplasia?6 cases?were collected.The expression of senescent cells in peripheral blood and lymph node tissues were detected by cell senescence staining;The morphology of cells in lymph nodes was observed by hematoxylin-eosin staining?HE?.The expression of p21^cip1ip1 protein,P16^INK4aNK4a protein,Rb protein and SENEX?ARHGAP18?proteinin in lymph node tissues were detected by immunohistochemistry Flow cytometry was used to detect the expression of CD4⁺T cells,regulatory T cells?Treg?,bone marrow-derived inhibitory cells?MDSCs?in lymph node tissues of the two groups.ELISA methods were used to detect the expression of IL-6,IL-8,IL-10,and TGF-?1 in tissue polishing fluid.All results were analyzed and plotted using SPSS 19.0 and Graphpad Prism6.Results:We found that the senescent cells in peripheral blood and lymph node tissues of patients with B-NHL were significantly increased compared with those with reactive lymph node hyperplasia,and the cells in lymph node tissues were significantly enlarged,the vacuoles increased,and the nucleus was oval,the cytoplasm lightly stained,which was consistent with the characteristics of senescent cells,indicating the presence of senescent cells in patients with B-NHL In addition,immunohistochemistry results showed that SENEX?ARHGAP18?protein,p21^cip1ip1 protein,P16^INK4aNK4a protein and Rb protein were significantly increased in lymph node tissues of B-NHL patients.Flow cytometry results suggested that patients with CD4⁺T cells decreased and Treg cells increased and the expression of MDSCs in peripheral blood increased relatively,indicating the immunosuppression of B-NHL patients.In addition,ELISA indicated that IL-6,IL-8,IL-10 and TGF-?1 were higher in the tissues of B-NHL patients than in the control group.Conclusion:1)SENEX gene-triggered cell senescence exists in B-NHL patients,2)SENEX gene may mediate aging through p53/p21^cip1ip1 and p16^INK4a/RB signaling pathways,3)Cell senescence may affect the microenvironment of tumors through SASP,which promot the occurrence and development of tumors.4)The senescence triggered by SENEX gene is closely related to B-NHL,but whether SENEX gene can be a new target for the treatment of B-NHL remains to be further studied.