| Objective:Hepatocellular carcinoma(HCC)is the fourth most common tumor and the third cause of death of cancer in China,with the poor prognosis and the high recurrence rate.The pathogenesis of HCC is still not very clear.It is generally considered that in the tumor microenvironment,the anti-tumor immunity is inhibited and the tumor is immune-escape-related.Myeloid-derived suppressor cells(Myeloid-derived suppressor cells,MDSCs)are important negative regulatory cells in the body,which can inhibit innate and adaptive immunity and may play an important role in tumor immune escape.This study will focus on the analysis of the expression of MDSCs in peripheral blood of patients with hepatocellular carcinoma caused by chronic hepatitis B(chronic hepatitis B,CHB)and the relationship with patients'clinical parameters,and the expression of interferon regulatory factor 8 in MDSCs of HCC patients was explored in order to find a new direction for immunotherapy of hepatocellular carcinoma.Methods:A total of 37 patients with HCC who were admitted to the Fifth Hospital of Shijiazhuang from April 2017 to January 2019,16 patients with CHB,and 21 healthy controls were collected.The clinical characteristics of HCC patients,as well as laboratory tests of liver function parameters and blood routine parameters were collected.Peripheral blood of all subjects were collected,peripheral blood mononuclear cells were isolated by density gradient centrifugation,and MDSCs and its subgroups in peripheral blood of three groups were examined.Analysis the expression of MDSCs and the distribution of MDSCs in patients with different clinical characteristics,the correlation between the expression of MDSCs and liver function parameters,and blood routine parameters.While detecting and comparing the expression of other relevant immune cells in peripheral blood,including CD4~+T cells,CD8~+T cells,Th1 cells,Th9 cells,Th17 cells,regulatory T cells(Tregs),Tc1cells,Tc9 cells and Tc17 cells,and the expression of IRF-8 was detected in MDSCs and analyzed,as well as its relationship with clinical characteristics and laboratory indicators.Statistical analysis was performed on the obtained data using SPSS 21.0.Result:1.The expression of MDSCs in peripheral blood of HCC patients,CHB patients and healthy controls were different(3.31%vs 1.06%vs 0.27%,?~2=57.742,P<0.001),and HCC patients were significantly higher than CHB patients(Z=-4.358,P<0.001),and healthy controls(Z=-6.923,P<0.001);the expression of G-MDSCs in peripheral blood of HCC patients,CHB patients and healthy controls were different(0.25%vs 0.11%vs 0.04%,?~2=26.168,P<0.001),among which HCC patients were significantly higher than healthy controls(Z=-5.108,P<0.001),and CHB patients were significantly higher than healthy controls(Z=-2.622,P=0.026),the expression of M-MDSCs in HCC patients,CHB patients and healthy controls were also different(0.93%vs 0.24%vs 0.16%,?~2=11.763,P=0.003).Among them,the HCC patients was significantly higher than the healthy controls(Z=-3.408,P=0.002).2.The expression of MDSCs in peripheral blood of patients with tumor metastasis was higher than that of HCC patients without metastasis(t=-2.196,P=0.035),and the expression of MDSCs in peripheral blood of HCC patients with advanced stage was higher than that of early patients(t=-2.196,P=0.035).The expression of MDSCs in peripheral blood of HCC patients was positively correlated with serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),direct indirect bilirubin(DBIL),lactate dehydrogenase(LDH),and negatively correlated with prealbumin(PA),as well as a positively correlated with monocyte counts.3.The expression of CD4~+T cells in peripheral blood of HCC patients,CHB patients and healthy controls was comparable(29.02%vs 31.05%vs29.38%,F=0.190,P=0.828),but there was a significant difference in CD8~+T cell expression(14.74%vs 21.04%vs 23.47%,?~2=6.295,P=0.043),in which HCC patients were significantly lower than healthy controls(Z=2.497,P=0.038);T cell subsets were compared,the expression of Th1 cells in HCC patients,CHB patients and health controls were different(6.23%vs 13.72%vs14.92%,F=5.020,P=0.013),among which HCC patients were significantly lower than CHB patients(t=-2.468,P=0.019),and HCC patients also significantly lower than the healthy controls(t=-2.981,P=0.005);there was a difference in the expression of Th9 cells between HCC patients,CHB patients and healthy controls(0.68%vs 0.38%vs 3.01%,?~2=15.246,P<0.001),the HCC group was significantly lower than the healthy controls(Z=2.980,P=0.009),and the CHB patients was also significantly lower than the healthy control(Z=3.608,P=0.001);the expression of Th17 cells in HCC patients,CHB patients and healthy controls were no statistical differences(2.29%vs1.63%vs 2.42%,?~2=1.231,P=0.540);There were differences in expression of Tregs in HCC patients,CHB patients,and health controls(1.02%vs 0.60%vs0.38%,?~2=10.032,P=0.007),among which HCC patients were significantly higher than healthy controls(Z=-3.034,P=0.007);There were differences in the expression of Tc1 cells compared HCC patients,CHB patients with healthy controls(8.78%vs 18.27%vs 28.90%,F=6.208,P=0.005),of which HCC patients were significantly lower than healthy controls(t=-3.513,P=0.001);There were differences in the expression of Tc9 cells between HCC patients,CHB patients and healthy controls(1.31%vs 0.89%vs 3.28%,?~2=10.139,P=0.006),and CHB patients were significantly lower than healthy controls(Z=3.160,P=0.005).There were differences in the expression of Tc17cells between HCC patients,CHB patients and healthy controls(3.68%vs1.11%vs 2.24%,?~2=10.703,P=0.005),among which HCC patients were significantly higher than CHB patients(Z=-3.246,P=0.004).4.The expression of MDSCs in peripheral blood of HCC patients was positively correlated with the expression of Tc1 cells(r=0.620,P=0.042).5.The expression of IRF-8 in MDSCs of HCC patients was significantly lower than that of healthy controls(0.98%vs 1.75%,t=3.800,P<0.001)and negatively correlated with serum AST(rs=-0.529,P=0.024),and there was no correlation with clinical indicators,blood routine parameters and other liver function parameters.Conclusions:1.The peripheral blood MDSCs and their subtypes of HCC patients were significantly increased.The more severe the HCC,the higher the expression of MDSCs,and along with liver damage.2.The expression of CD8~+T cells in peripheral blood of HCC patients was significantly decreased,and the expression of Th1 cells,Tc1 cells,Th9cells and Tc9 cells were all decreased.While the expression of Tregs and Tc17cells was significantly increased.3.The expression of IRF-8 in MDSCs was decreased in HCC patients,suggesting that IRF-8 may be an important transcription factor for negative regulation of MDSCs expansion and function. |
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