The Expression And Significance Of PD-1 In T Cells Of Patients With Acute Leukemia

Background:Acute leukemia(AL)is a kind of malignant clonal disease of hematopoietic stem cells.With the improvement of medical treatment in recent years and the application of new therapies,prognosis has made some progress.However,acute myeloid leukemia(AML),the most common type of leukemia in acute leukemia,has shown no significant change in treatment and prognosis over the past 40 years,with a 5-year overall survival rate of From 6.3%(1975-1980)to 23.9%(2007-2012).The survival of adult acute B lymphoblastic leukemia has indeed achieved a significant increase since the advent of CAR-T cell therapy,but the survival rate of T-ALL has not changed significantly.Programmed death-1(PD-1,CD279)is an inhibitory receptor that contains the immunoreceptor tyrosine-inhibiting motif and the immunoreceptor tyrosine-switching motif domain.PD-1 and its programmed death ligand 1(PD-L1)and programmed death ligand 2(PD-L2)are members of CD28 / B7 family.Negative regulation of tumor immune response by PD-1 / PD-L1 pathway is a hot topic in recent years.PD-1 has also been found to be overexpressed on immune cells in many newly diagnosed hematologic and solid tumor patients,and anti-PD-1 antibodies are currently in clinical trials and have achieved some efficacy.However,a significant proportion of patients are still ineffective.Therefore,it is necessary to further explore the expression of PD-1 during AL treatment and its relationship with therapeutic effect,so as to provide more powerful evidence for the clinical application of anti-PD-1 antibody in the treatment of AL.Objective:In this study,we examined the expression of PD-1 on the surface of T lymphocytes in patients with newly diagnosed acute leukemia and compared the differences in the expression of T cell surface between AL patients and newly diagnosed AL patients.Methods:The proportion of CD4 +,CD8 + T cells in peripheral blood and the expression of PD-1 on peripheral blood of 89 AL patients and 26 healthy controls were detected by flow cytometry and analyzed.Among the 89 patients,There were 49 AML and 40 ALL.Of the 49 AML patients,14 were newly diagnosed,including 6 males and 8 females,with a median age of 53.5 years.Thirty-five patients were referred for remission,including 13 patients(4 males and 9 females)with complete remission(CR),with a median age of 51.3 years.Twenty-two patients(11 males and 11 females)without remission(NR)with a median age of 53.2 years old.Of the 40 ALL patients,11 were newly diagnosed,including 5 males and 6 females,with a median age of 46.6 years.Of the 29 patients who were referred,there were 11 patients(5 males and 6 females)with complete remission(CR),with a median age of 48.6 years.Eighteen patients(10 males and 8 females)without remission(NR)with a median age of 47.2 years old.A total of 26 healthy control group,including 12 males and 14 females,with a median age of 35.1 years.There was no significant difference in gender and age among all groups.Results:Compared with the healthy control group,the proportion of CD4 + T cells in lymphocytes and the ratio of CD4 / CD8 in newly diagnosed AML and ALL patients were significantly decreased(P <0.05)and the proportion of CD8 + T lymphocytes in lymphocytes was significantly increased(P < 0.05).Compared with the newly diagnosed group,the ratio of CD4 + T cells to lymphocytes and the ratio of CD4 / CD8 in CR patients after AML and ALL treatment were significantly increased(P <0.05).After treatment,the proportion of CD8 + T cells in lymphocytes in CR group were significantly decreased(P <0.05).There was no significant change in NR group after ALL treatment.PD-1 expression in peripheral blood CD4 + T cells and CD8 + T cells in newly diagnosed AML and ALL patients were significantly higher than those in healthy controls.After treatment,The expression of PD-1 in peripheral blood CD4 + T and CD8 + T cells in AML and ALL patients in CR group were significantly lower than those in the newly diagnosed group(P <0.05).After treatment,the expression of PD-1 in CD4 + T cells in AML and ALL patients There was no significant difference between the NR group and the newly diagnosed group,but significantly higher than the healthy control group(P <0.05).The serum IL-10 concentration in the newly diagnosed AML group was significantly higher than that in the healthy control group(P<0.05).The serum IL-10 concentration in the newly diagnosed ALL group was significantly higher than that in the healthy control group,but there was no statistical significance;the serum in the newly diagnosed AML group and ALL group.IFN-? was significantly higher than the healthy control group(P<0.05),but serum IL-2 was almost undetectable,suggesting that serum levels of cytokines were abnormal in newly diagnosed AL patients.Conclusions:PD-1 is highly expressed on the surface of CD4 + and CD8 + T cells in newly diagnosed AL patients.At the same time,the expression of PD-1 is closely related to the therapeutic effect in patients,suggesting that PD-1 / PD-L1 immunosuppressive pathway plays an important role in the occurrence and development of acute leukemia Which has provided a new idea for the clinical application of anti-PD-1 antibody in the treatment of AL.However,the clinical application of anti-PD-1 antibody in the treatment of AL still requires more clinical trials to explore.