Research On The Expression Of PD-1,CTLA-4 And Cytokines In Acute Myeloid Leukemia Treated By Microtransplantation

Objective:To explore the immune mechanism of microtransplantation on acute myeloid leukemia(AML),we evaluated the expression of programmed cell death protein 1(PD-1),cytotoxic T lymphocyte-associated antigen 4(CTLA-4)on the following T-cell subsets:CD4~+T cells?CD8~+T cells and regulatory T cells(Treg),interferon-?(IFN-?),tumor necrosis factor-alpha(TNF-a),interleukin-2(IL-2),interleukin-10(IL-10)and interleukin-10(IL-6)in peripheral blood of patients with low and medium-risk AML before and after microtransplantation,Then we analyzed the change and relativity between PD-1,CTLA-4 and the cytokines.Methods:We collected 18 patients with low and medium-risk AML who received microtransplantation treatment for three or more courses and 11 cases of healthy donors were enrolled in this study.The expression of PD-1,CTLA-4 on T-cell subsets and the concentration of cytokines IFN-?,TNF-a,IL-2,IL-10,IL-6were detected by flow cytometry.We also analysis the relativity of PD-1,CTLA-4and the cytokines.Results:1.There was a significantly higher expression of PD-1 on CD4~+T cells(17.09±1.96%vs 4.11±0.70%,P<0.001),CD8~+T cells(14.47±2.13%vs 3.94±0.44%,P<0.01),Tregs(19.09±4.02%vs 4.45±0.37%,P<0.001)of patients with low and medium-risk AML before microtransplantation compared with healthy donors;There was a significantly lower expression of PD-1 on CD4~+T cells(9.49±1.11%vs17.09±1.96%,P<0.001),CD8~+T cells(4.19±1.81%vs14.47±2.13%,P<0.001),Tregs(8.66±0.96%vs 19.09±4.45%,P<0.001)of AML patients after microtransplantation compared with the patients before microtransplantation.2.There was a significantly higher expression of CTLA-4 on CD4~+T cells(4.51±0.55%vs 2.12±0.78%,P<0.001),CD8~+T cells(6.33±1.08%vs1.46±0.42%,P<0.001),Tregs(14.49±2.45%vs 2.47±0.39%,P<0.001)of patients with low and medium-risk AML before microtransplantation compared with healthy donors;There was a significantly lower expression of CTLA-4 on CD4~+T cells(3.87±0.67%vs 4.51±0.55%,P<0.05),CD8~+T cells(6.33±1.08%vs 1.46±0.42%,P<0.001),Tregs(5.64±0.80 vs 14.49±2.45%,P<0.001)of AML patients after microtransplantation compared with the patients before microtransplantation.3.The level of IFN-?and IL-2 in peripheral blood of patients with low and medium-risk AML before microtransplantation decreased significantly compared with healthy donors(3.38±0.53 vs 4.90±0.58,3.16±0.48 vs 4.11±0.48,P<0.01);The level of TNF-?,IL-6 and IL-10 in peripheral blood of patients with low and medium-risk AML before microtransplantation increased significantly compared with healthy donors(20.32±1.46 vs 5.56±0.63,14.49±2.45 vs 2.47±0.39,19.96±1.34vs 4.19±0.28,P<0.01);The level of IFN-?and IL-2 in peripheral blood of patients with low and medium-risk AML after microtransplantation increased significantly compared with before microtransplantation(6.87±0.93vs3.38±0.53,5.82±1.03vs 3.16±0.48,P<0.01);The level of TNF-?,IL-6 and IL-10 in peripheral blood of patients with low and medium-risk AML after microtransplantation decreased significantly compared with before microtransplantation(9.15±0.91 vs20.32±1.46,6.75±4.11 vs 14.49±2.45,8.16±1.35vs 19.96±1.34,P<0.01).4.The expression of PD-1 on CD4~+T cells in AML patients before microtransplantation was negatively related to the level of IFN-?and IL-2;The expression of PD-1 on CD8~+T cells in AML patients before microtransplantation was negatively related to the level of IFN-?and IL-2;The expression of PD-1 on Treg,CTLA-4 on CD4~+T cells and Treg in AML patients before microtransplantation was positively related to the level of IL-10.Conclusion:1.The increased expression of PD-1 and CTLA-4 on T-cell subsets in low and medium-risk AML before microtransplantation,suggesting that PD-1 and CTLA-4 concerning in AML immune disorder.2.The level of TNF-?,IL-6 and IL-10were increased,while the level of IFN-?,IL-2 were decreased in low and medium-risk AML and related to PD-1 and CTLA-4 on T lymphocyte subsets,suggesting that PD-1and CTLA-4 together with TNF-?,IL-6,IL-10,IFN-?and IL-2 participate in pathomechanism of AML.3.The expression of PD-1 and CTLA-4 on T-cell subsets of AML patients was decreased,and the level of TNF-?,IL-6,IL-10 were decreased,and the level of IFN-?,IL-2 were increased in AML patients after microtransplantation,suggesting that microtransplantation can recover the immunosuppressive tumor microenvironment of AML.