The Effects Of The Cellular Immunotherapy On The Expression Of CXCR1,CXCR2 And CXCL8 In Hepatocellular Carcinoma

Objective:To investigate the expression of CXCR1/2 and CXCL8 in hepatocellular carcinoma(HCC)patients after cellular immunotherapy.Method:35 typical HCC cases were divided into 24 cases in T2 staging and 11 cases in T3 staging according to computerized tomographic scanning(CT)of hepatic lesions and the TNM staging standards of HCC published by the American Joint Committee on Cancer(AJCC)in 2010,the serum levels of CXCL8 and GP-73 were measured by enzyme-linked immunosorbent assay(ELISA);Peripheral blood neutrophils(PBNs)were separated by density gradient solution.CXCR1/2 and CXCL8 mRNA in PBNs and local lesions of HCC patients were detected by PCR.8 patients were treated with CIK therapy,the CXCR1/2 and CXCL8 mRNA levels of T2/T3 staging patients were observed.Results:The serum content of CXCL8 in HCC patients was(315.66�100.85)pg/mL,and the serum content of GP-73 was(214.84�49.11)ng/mL,the difference was statistically significant compared to normal control group(P<0.0001).PCR results of PBNs demonstrated that CXCR1 mRNA levels on normal control group,non-CIK treatment group and CIK treatment group were(0.662�0.0678),(1.1333�0.0551)and(0.87�0.0563)lgGAPDH/lgcDNA respectively;CXCR2 mRNA levels on normal control group,non-CIK treatment group and CIK treatment group were(0.605 �0.0628),(0.8863 � 0.0605)and(0.76 � 0.0428)lgGAPDH/lgcDNA respectively;CXCL8 mRNA levels on normal control group,non-CIK treatment group and CIK treatment group were(0.881 � 0.0617),(1.2007�0.073)and(1.095�0.064)lgGAPDH/lgcDNA respectively.Univariate analysis of variance showed a significant difference between the three groups(P<0.0001);HE staining of HCC sections revealed that the HCC cells was significantly enlarged,the nucleus shape is variable and irregular,the phenomenon of mitosis is increased,the cells overlapped with each other and the outline is blurred,the neovascular was observed in the tumor tissue;the levels of CXCR1/2 and CXCL8 mRNA in 14 cases of resected tissue were significant higher than the normal control group(t=6.528,P<0.0001;t=9.583,P<0.0001;t=7.832,P<0.0001).The levels of CXCR1/2 and CXCL8 mRNA in resected tissue from HCC T2 staging patients were(0.4462�0.0984),(1.0509�0.1262)and(0.9032�0.1095)lgGAPDH/lgcDNA respectively,and the levels of CXCR1/2 and CXCL8 mRNA in T3 staging patients were(0.8296 � 0.1628),(1.1361 � 0.1888)and(1.2649 � 0.2357)lgGAPDH/lgcDNA,the expression of CXCR1 and CXCL8 mRNA in patients between T2 staging and T3 staging patients were significantly different(t=4.341,P=0.0010;t=2.893,P=0.0135),no significant changes were observed in the levels of CXCR2 mRNA between T2 staging and T3 staging patients(t=0.8215,P=0.4274).HE staining of HCC sections showed that lots of hypochromatic erythrocytes appeared in the lumen,suggesting that neovascular was generated in the lesions.Conclusion:The serum contents of CXCL8 and GP-73 in HCC patients were significantly increased,also the levels of CXCR1/2 and CXCL8 mRNA in PBNs and HCC biopsy tissues were increased significantly,indicating that high levels of CXCL8 in the serum could recruit PBNs and other cells to participate in the systemic inflammatory response,but also promote the neovascularization at the lesions and the spread of CXCR1/2 to systemic vascular.The levels of CXCR1/2 and CXCL8 mRNA in peripheral blood from HCC patients were significantly decreased after CIK therapy,However,there was no significant difference in CXCR2 mRNA levels between HCC biopsy tissues and normal tissues,suggesting that CXCR1/2 and CXCL8 seem to play a pivotal role in the tumorigenesis and progression of HCC,CIK theapy may exert effects on repressing local inflammatory response and tumorigenesis.