Font Size: a A A

Differential Expression And Clinical Significance Of PD-1 In Relapaed Or Refractory Multiple Myeloma

Posted on:2019-07-28Degree:MasterType:Thesis
Country:ChinaCandidate:L ZhangFull Text:PDF
GTID:2544305450451424Subject:Clinical Medicine Internal Medicine
Abstract/Summary:
Background and Objective Multiple myeloma(MM)is a cytoplasmic clonal proliferative disease derived from terminal differentiation of B lymphocytes,characterized by bone marrow being replaced by malignant plasma cells,bone destruction and abnormal immunoglobulin production.The annual incidence of MM is 2 to5/100,000,10 to 15 percent of tumors in the blood system,which have surpassed leukemia and are called second only to non Hodgkin’s lymphoma.This disease often occurs in the middle and old age.The average age of onset is about 70 years,and the ratio of male to female is 1.6-3:1.Most of the cases are primary,the etiology of which is still unclear,such as ionizing radiation,exposure to chemical poisons,chronic antigen stimulation,autoimmune diseases,heredity,virus infection(human herpesvirus type 8,HHV-8)and so on.However,there is not enough evidence to prove and a small part of the development of monoclonal gamma globulin disease(MGUS).Multiple myeloma is still an incurable cytoplasmic clonal proliferative disease.In recent years,because of the use of new drugs,such as bortezomil,renalidomide and its derivatives,the survival rate and remission rate of patients with multiple myeloma have been greatly improved,but recurrence/refractory is still the common cause of death of multiple myeloma.The nature of MM disease is plasmacyte tumor.The occurrence of tumor is a complex process involving multiple genes and multiple steps,.immune disorders,especially immune escape,is very important in the occurrence and development of tumors.The main mechanism of tumor immune escape is the induction and apoptosis of antigen-specific T cells,costimulatory molecules and their corresponding regulatory systems are involved in this process.The B7 family is an important costimulatory molecule in immune response,B7-H1,also known as programmed cell death ligand-1,is an important member in the B7 family,the study of the B7 family has become a hot research trend of the last few years.In recent years,it has been confirmed that the expression of PD-L1 is increased in a variety of tumor cells and tumor tissues,and the antitumor immune response can be reduced when PD-L1 combined with programmed cell death-1(PD-1).At present the research about PD-1,PD-L1 mainly focused on solid tumors,and is less on blood disease.The domestic research reports,the establishment of mouse model of MM transgenic mice,and then use flow cytometry to detecte the expression of PD-1 on T cell in bone marrow and spleen,compared with wild-type mice,PD-1 significantly increased.There are many studies abroad suggest that in peripheral blood of MM patients,the expression of PD-1 and PD-Ll was higher than the normal group,and the difference was significant(P<0.05).At present,there are few studies of the relationship between MM and PD-1 in our country.The purpose of this study was to detect the expression of PD-1 in peripheral blood in patients with recurrence/refractory MM,and to explore the relationship between PD-1 and the clinical classification,compare the difference and correlation so as to provide experimental basis and theoretical support for the future clinical treatment of recurrence/refractory MM.Methods To collect 30 patients with recurrent/refractory multiple myeloma in our hospital from April 2016 to October 2017,including 18 cases of IgG,10 cases of IgA and 2 cases of light chain.30 healthy persons with normal physical examination in our hospital.The average expression level of CD4+T cells and CD8+ T cells in peripheral blood T cells was detected by flow cytometry.After 4 courses of treatment,the average expression level of CD4+T cells and CD8+ T cells in peripheral blood was tested again.SPSS 17.0 statistical software was used to analyze the results,and Graphpad prism 5 software was selected.Results 1.The peripheral blood CD4+T cells in patients with recurrence/refractory MM PD-1 the average expression rate was(28.09+6.75)%,healthy persons CD4+T cells,the average expression rate for PD-1 was(5.93+0.94)%,CD8+ T cells in patients with recurrence/refractory MM PD-1 the average expression rate was(16.40+4.79)%,healthy persons peripheral blood CD8+ T cells,PD-1 the average expression rate was(2.86+0.92)%,relapse/refractory MM patients peripheral blood CD4+PD-1+and the healthy physical examination of peripheral blood CD4+ PD-1+ comparison,relapse/refractory MM patients CD8+ PD-1+ average expression rate and the healthy persons of CD8+PD-1+ the average expression rate comparison,both have significant difference(P<0.05);2.After 4 courses oftreatment,the positive rate of pd-1 on peripheral blood T cells of the patient was decreased before and after treatment,and the difference was statistically significant(P<0.05).Conclusion In this study,we found that the level of PD-1 expression of CD4 T cells in peripheral blood of recurrent/refractory MM patients was significantly higher than that of healthy controls,After four courses of treatment,the positive rate of PD-1 were decreased,but the PD-1 drop degree is different,and the higher the PD-1 expression level,the worse the response to chemotherapy and the worse the prognosis.The higher the malignancy of the disease,the higher the expression of PD-1,which suggests that PD-1 may be related to the clinical outcomes of MM and the progression of the disease.It is further speculated that the PD-1/PD-L1 signaling pathway may be involved in the immune escape of MM.To provide the corresponding theoretical basis for the clinical immunotherapy of MM in the future.
Keywords/Search Tags:Multiple myeloma, PD-1, Flow cytometry, Immunotherapy
Related items