Application Value Of Immune Score Based On CTLs,TANs And TIPs In Prognosis Of Hepatocellular Carcinoma

Object To investigate the clinical application value of CTLs,TANs and TIPs in the immune microenvironment in the prognosis of patients with hepatocellular carcinoma.Methods The general clinical and pathological data of 142 patients with hepatitis Brelated hepatocellular carcinoma who underwent radical surgical resection from June2017 to January 2019 in the Department of Hepatobiliary Surgery of the X Affiliated Hospital of Bengbu Medical College were retrospectively analyzed.The general clinical data included: Gender,age,liver cirrhosis,ascites,blood biochemical indexes（ALT,AST,GGT,TBIL,ALB）,lymphocyte count,neutrophil count,PLT level,tumor indexes（AFP,tumor number,tumor diameter）,pathology diagnosis（tumor properties,density of Tumor-associated cytotoxic lymphocytes（CTLs）,tumor-associated neutrophils（TANs）,tumor-infiltrating platelets（TIPs）in central tumor（CT）and Invasive margin（IM）tissue）.Immunohistochemical staining of CTLs,TANs,and TIPs with CD8,CD66 b,and CD42 b,respectively.The NLR,PLR,infiltrating neutrophilsto-lymphocyte ratio（i NLR）,and infiltrating platelet-to-lymphocyte ratio（i PLR）were calculated through the above indicators.The expression of CTLs,TANs and TIPs in CT and IM tissues were analyzed by Spearman test,and detecting the correlation with counts of lymphocytes,neutrophils and platelets in peripheral blood.The receiver operating characteristic curve（ROC）was used to calculate the best cut-off value of NLR,PLR,i NLR and i PLR,and the area under the AUC curve was used to compare its judgment in the ability of survival prognosis.Univariate and multivariate analysis of survival prognosis were carried out by COX proportional hazards model.K-M survival curve and log-rank test were used for survival analysis.Results The number of CTLs、TANs in the CT tissue was lower than that in the IM tissue,while the number of TIPs in the tissue of CT and IM was converse.The correlation analysis showed that the expression of CTLs in the IM tissue was positively correlated with the peripheral blood lymphatic count（r=0.297,P <0.001）,the amount of TANs in cancer tissue and adjacent tissue was correlated with peripheral blood neutrophil count（CT: r=0.581,P<0.001,IM: r=0.536,P<0.001）,while the expression of TIPs in CT tissue was negatively correlated with peripheral blood platelet count（r=-0.178,P=0.034）.The increased infiltration density of tumor-related CTLs will significantly prolong the OS and RFS of patients at 3 years after surgery,while the infiltration of TANs increases the number of patients with poor prognosis.High infiltration of TIPs in cancer tissue suggests a poor prognosis.According to the ROC analysis,the best cut-offs for NLR,PLR,CT-i NLR,IM-i NLR,CT-i PLR,and IM-i PLR were 3.15,114.50,0.80,0.45,1.12,and 0.13,respectively,and the areas under the AUC curve were 0.661,0.630,0.692,0.736,0.780,0.650,the K-M survival curve shows that the levels of NLR,PLR,CT-i NLR,IM-i NLR,CT-i PLR,and IM-i PLR are related to the postoperative prognosis of patients,the higher score with the shorter of 3-year OS and RFS.Univariate analysis found that AST,ALB,tumor diameter,liver cirrhosis,AFP,Child grade,BCLC stage,NLR,PLR,i NLR,i PLR were associated with the prognosis of HCC patients.Liver cirrhosis,AFP,Child grade,BCLC stage,NLR,PLR,i NLR,i PLR are independent risk factors affecting the survival of patients with liver cancer.Conclusion1.The infiltration density of CTLs,TANs and TIPs in the immune microenvironment was correlated with peripheral blood lymphocyte count,neutrophil count and platelet count to a certain extent.The number of CTLs and TANs in cancer tissues was lower than that in para-cancer tissues.CTLs was positively correlated with the number of peripheral blood lymphocytes,while TANs was positively correlated with the number of peripheral blood neutrophils in cancer tissues and para-cancer tissues.The number of TIPs in cancer tissues was significantly higher than that in adjacent tissues,and was negatively correlated with peripheral blood platelet count.2.The infiltration density of CTLs,TANs and TIPs in the immune microenvironment are prognostic factor for predicting 3-year OS and RFS in HCC patients.In the tumor microenvironment,increased infiltration of CTLs was associated with better prognosis,while increased infiltration of TANs and TIPs in tumor tissue was associated with poorer prognosis.3.The prognostic models（i NLR,i PLR）established by CTLs,TANs and TIPs are independent risk factors affecting the postoperative prognosis of HCC patients.The larger the i NLR and i PLR values,the shorter the postoperative 3-year OS and RFS of the patients,the higher predictive power of i NLR and i PLR compared with the corresponding peripheral blood prognostic models（NLR,PLR）that have been proved to be related to prognosis.