Study On The Prognostic Value Of Tumor Interstitial Infiltrating Lymphocytes In Intrahepatic Bile Duct Cell Carcinoma

BACKGROUND: Intrahepatic cholangiocarcinoma ICC is a serious lesion caused by malignant change of intrahepatic bile duct epithelial cells.It is the second most common primary liver malignancy after hepatocellular carcinoma.In recent years,the morbidity and mortality of the ICC has been on the rise in almost all countries.Clinically,surgical resection is the only effective treatment for early ICC.However,due to the high recurrence rate,the prognosis of ICC patients undergoing radical resection is still very poor.Those who lost the chance of operation or could not have surgery had poor prognosis,and few long-term survivors.Compared with other primary liver malignancies,patients with ICC have shorter survival,lower radical resection rates and lower cure rates.In recent years,the presence of tumor infiltrating immune cells in tumor microenvironment has predictive significance for many solid tumors.Studies on tumor infiltrating lymphcells(TILs)indicate that the presence of TILs is a good indicator of postoperative prognosis of patients.The international working group on TILs recently recommended standardized analysis of hematoxylin and eosin(HE)stained sections to assess the role of TILs in breast cancer.There has been evidence-based medical evidence that TILs in the tumor microenvironment is significantly associated with the prognosis of patients with a variety of malignancies.However,studies of TILs in intrahepatic cholangiocarcinoma have not been reported.Therefore,we intended to analyze the predictive value of TILs and clinical parameters in tumor tissues of ICC patients for progression-free survival and overall survival after complete resection of ICC patients.The identification of additional prognostic factors to predict progression-free survival and overall survival of ICC patients after complete resection is of great significance for clinical development of treatment strategies and selection of appropriate individualized treatment regimens.Objective: The predictive value of TILs invasion and clinical parameters in tumor tissues of ICC patients for progression-free survival and overall survival after complete resection of ICC patients was analyzed.Additional prognostic factors were identified to predict progression-free survival and overall survival of ICC patients after complete resection,providing a basis for clinical treatment strategy formulation and selection of appropriate individualized treatment regiments.Methods: According to certain admission criteria,68 patients with ICC who underwent radical resection were included in this study.We investigated the density of TILs in tumor tissues of ICC patients who underwent radical resection and scored them by HE-stained pathological sections.The clinical data and prognosis of ICC patients were obtained by consulting the patient's clinical history and follow-up,and finally statistical analysis of these data.Results: In this study,a total of 68 patients who were diagnosed with ICC in our hospital and underwent radical surgical resection were included,including 38 males and 30 females,aged 35-80 years with an average age of 60.28 years.The diagnosis of these patients has been confirmed clinically and pathologically.Thirty-two of the 68 patients were found to be TILs positive and the remaining 36 were TILs negative.In ICC patients,higher CA125(HR=1.65,95%ci 1.06-2.61,p=0.02),higher CA199(HR=1.74,95%ci: 1.21-2.94,p=0.03)and negative TILs(HR=2.84,95%ci: 1.48-5.46,p<0.01)were important independent predictors of overall survival(OS).TILs density was also associated with OS in ICC patients(p<0.01).The ICC TILs in tumor tissues in patients with negative(HR = 2.88,95% CI: 1.44 5.76,p < 0.01)was progression-free surial(Progressives Free Survival,PFS)important independent predictor.Progression-free survival curves also demonstrated the predictive value of TILs in tumor tissues of ICC patients(p<0.01).Low TILs density in tumor tissues of ICC patients was associated with increased CA125(P=0.03)or CA199(P<0.01)levels.ICC patients with negative TILs in tumor tissues were oftenaccompanied by higher CA199 level(P=0.05),higher tumor differentiation degree(P=0.02),larger tumor diameter(P=0.05),positive bile duct/vascular tumor thrombi(P=0.03),positive satellite metastasis(P=0.02),etc.,which were not correlated with gender,age,tumor site,lymph node metastasis,AJCC stage and nerve invasion.Conclusion: Our data suggest that TILs negative in tumor tissues of ICC patients is an independent predictor of poor OS and poor PFS.Low TILs density in tumor tissues was associated with increased CA125(P=0.03)or CA199(P<0.01)levels.Through comprehensive analysis,we conclude that TILs in tumor tissues of ICC patients have certain guiding significance in predicting progression-free survival(PFS)and overall survival(OS)of ICC patients after radical resection.