| Objective : This study aimed at detecting the changes of expression of programmed death-1(PD-1)and cytotoxic T lymphocyte-associated antigen 4(CTLA-4)on CD3+T cell,CD4+T cell,CD8+T cell,Treg cell and the changes of levels of interferon-?(IFN-?),interleukin-10(IL-10),tumor necrosis factor-afar(TNF-?),interleukin-4(IL-4),and transforming growth factor beta(TGF-?)in patients with high-risk myelodysptastic syndrome(MDS)before and after treatment with decitabine combined with thalidomide.To analyze the correlation between PD-1,CTLA-4 on T cell subsets and cytokines and its clinical significance.Methods: Collected 18 cases of different subtypes of newly diagnosed high risk MDS patients treated with decitabine combined thalidomide for three or more courses(including three courses).12 healthy controls were enrolled in the study.The expression levels of PD-1 and CTLA-4 on CD3+T cell,CD4+T cell,CD8+T cell and Treg cell in peripheral blood of MDS patients and healthy controls were detected by flow cytometry.Meanwhile,the levels of cytokines IFN-?,IL-4,IL-10,TNF-? and TGF-? in peripheral blood of MDS patients and healthy controls were tested by enzyme linked immunosorbent assay(ELISA).And further analysis of T cell subsets expressed PD-1,CTLA-4 and the correlation between cytokines.Results: 1.The expression of PD-1 on CD3+T cells in peripheral blood of high risk MDS patients before treatment was higher than that of the normal control group(19.74 ± 2.08% vs 5.28± 1.60%,P <0.001),The expression of PD-1 on CD4+T cells in peripheral blood of high risk MDS patients before treatment was significantly higher than that of the normal control group(35.35±2.49% vs 2.64±0.79%,P<0.001),The expression of PD-1 on CD8+T cells in peripheral blood of high risk MDS patients before treatment was significantly higher than that of the normal control group(24.50 ± 1.47% vs 3.46 ± 0.31%,P <0.001),and the expression of PD-1 on Tregcells in peripheral blood of high risk MDS patients before treatment was significantly higher than that of the normal control group(41.31±4.50% vs 5.01±1.79%,P<0.001),the differences were statistically significant.The expression of PD-1 on CD3+T cells in patients after treatment was significantly decreased comparing with patients before treatment(8.21 ± 2.20% vs 19.74 ± 2.08%,P <0.001),The expression of PD-1 on CD4+T cells in patients after treatment was significantly decreased comparing with patients before treatment(6.64±1.52% vs 35.35±2.49%,P<0.001),The expression of PD-1 on CD8+T cells in patients after treatment was significantly decreased comparing with patients before treatment(5.61±1.12% vs 24.50±1.47%,P <0.001),The expression of PD-1 on Treg cells in patients after treatment was significantly decreased comparing with patients before treatment(7.68±1.73% vs 41.31±4.50%,P<0.001),the differences were statistically significant.2.The expression of CTLA-4 on CD3+T cells in peripheral blood of high risk MDS patients before treatment was higher than that of the normal controls(9.71±1.45% vs0.46±0.57%,P<0.001),The expression of CTLA-4 on CD4+T cells in peripheral blood of high risk MDS patients before treatment was higher than that of the normal controls(3.68±1.17% vs 0.70±0.58%,P<0.01),The expression of CTLA-4 on CD8+T cells in peripheral blood of high risk MDS patients before treatment was significantly higher than that of the normal controls(7.64±1.69% vs1.51±0.61,P<0.001),The expression of CTLA-4 on Treg cells in peripheral blood of high risk MDS patients before treatment was significantly higher than that of the normal controls(14.57±1.87% vs 2.69±1.44%,P<0.001),the differences were statistically significant.The expression of CTLA-4 on CD3+T cells in patients after treatment was significantly decreased comparing with patients before treatment(2.42±1.09% vs 9.71±1.45%,P<0.001),The expression of CTLA-4 on CD4+T cells in patients after treatment was decreased comparing with patients before treatment(1.96±0.23% vs 3.68±1.17%,P<0.001),The expression of CTLA-4 on CD8+T cells in patients after treatment was decreased comparing with patients before treatment(3.57±0.96% vs 7.64±1.69%,P<0.001),The expression of CTLA-4 on Treg cells in patients after treatment was significantly decreased comparing with patients before treatment(6.43±1.98% vs14.57±1.87%,P<0.001),the differences were statistically significant.3.The level of IFN-? in peripheral blood of MDS patients before treatment was higher than that in the normal controls(10.61±1.47 vs 5.59±0.36,P<0.001),The level of TGF-? in peripheral blood of MDS patients before treatment was higher than that in the normal controls(29.53±1.60 vs 16.74±1.16,P<0.001),The level of IL-4 in peripheral blood of MDS patients before treatment was higher than that in the normal controls(11.58±1.86 vs 7.66±1.05,P<0.001),The level of TNF-? in peripheral blood of MDS patients before treatment was statistically higher than that in the normal controls(24.27±0.88 vs 7.05±0.78,P<0.001),The level of IL-10 in peripheral blood of MDS patientsbefore treatment was statistically higher than that in the normal controls(78.39±2.38 vs 9.63±0.38,P<0.001)the differences were statistically significant.The level of IFN-? in peripheral blood of MDS patients after treatment was lower than that in patient before treatment(7.63±1.28 vs10.61±1.47,P<0.001),The level of IL-4 in peripheral blood of MDS patients after treatment was lower than that in patient before treatment(9.35±1.09 vs 11.58±1.86,P<0.001),The level of TGF-? in peripheral blood of MDS patients after treatment was significantly lower than that in patient before treatment(19.48±1.50 vs 29.53±1.60,P<0.001),The level of TNF-? in peripheral blood of MDS patients after treatment was lower than that in patient before treatment(10.45±0.49 vs 24.27±0.88,P<0.001),The level of IL-10 in peripheral blood of MDS patients after treatment was significantly lower than that in patient before treatment(15.65±1.00 vs 78.39±2.38,P<0.001),the differences were statistically significant.4.The expression of PD-1 on CD8+CD25-T cell and the level of IFN-? and in patients before treatment was positively correlated(r=0.876,P<0.01),The expression of PD-1 on CD4+T cell and the level of IFN-? and in patients before treatment was positively correlated(r=0.538,P<0.05),The expression of PD-1 on CD3+T cell and the level of IFN-? and in patients before treatment was positively correlated(r=0.499,P<0.05),The expression of PD-1 on Treg cell and the level of IFN-? and in patients before treatment was positively correlated(r=0.921,P<0.001).The expression of CTLA-4 on CD3+T cell and the level of IL-10 and in patients before treatment was positively correlated(r=0.885,P<0.001),The expression of CTLA-4 on CD4+T cell and the level of IL-10 and in patients before treatment was positively correlated(r=0.781,P<0.001),The expression of CTLA-4 on CD8+T cell and the level of IL-10 and in patients before treatment was positively correlated(r=0.803,P<0.001),The expression of CTLA-4 on Treg cell and the level of IL-10 and in patients before treatment was positively correlated(r=0.726,P<0.001),the differences were statistically significant.Conclusions: 1.The expression of PD-1 and CTLA-4 on CD3+T cell,CD4+T cell,CD8+ T cell and Treg cell were significantly higher in patients with high risk MDS before treatment,T cells immune dysfunction may be involved in the pathogenesis of MDS.2.The level of cytokines IFN-?,IL-4,TGF-?,TNF-? and IL-10 were significantly higher in patients with high risk MDS before treatment,Changes of cytokine levels in immune microenvironment are involved in the pathogenesis of MDS.3.The expression of PD-1 and CTLA-4 on the T cell subsets were positively correlated with the levels of cytokines IFN-? and IL-10 in peripheral blood of patients with high risk MDS before treatment,Suggesting that cytokines IFN-? and IL-10 have a synergy with PD-1 and CTLA-4 expressed on T cells in the pathogenesis of MDS. |
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