Tumor-Infiltrating Lymphocytes and Macrophages in Intrahepatic Cholangiocellular Carcinoma. Impact on Prognosis after Complete Surgery

BackgroundImmune infiltrate impacts prognosis of several tumors. To assess the prognostic impact of tumor-infiltrating lymphocytes and macrophages in patients undergoing resection for intrahepatic cholangiocellular carcinoma (ICC).MethodsAll consecutive patients undergoing surgery for ICC between 2008 and 2016 were considered. Inclusion criteria were complete resection and follow-up >12 months. Tissue sections were immunostained for CD3+, CD4+, CD8+, Foxp3+, and CD68+. The number of positive cells was quantified using a computer-aided image analysis system. Different cut-off values were tested as predictors of overall survival (OS).ResultsFifty-three patients were analyzed. ICC were T1 in 28 patients, multifocal in 11, and N+ in 13. After a median follow-up of 42 months, 5-year OS was 52.1%. The following immune infiltrate values were associated with better OS: CD3+ >0.10% (5-year OS 63.3% vs. 13.6% if <= 0.10%, p =0.001); CD8+ >0.10% (56.2% vs. 28.6% if <= 0.10%, p =0.051); Foxp3+ absent (59.4% vs. 16.0% if present, p =0.049). CD4+ and CD68+ infiltrates were not associated with OS. Three-year OS rates in patients with 0, 1, and >= 2 negative prognostic factors were 73.6%, 47.3%, and 14.3%, respectively (p <0.001). CD3+ infiltrate stratified prognosis in T1 tumors (3-year OS 71.7% if CD3+ >0.10% vs. 14.3% if <= 0.10%, p <0.001).ConclusionsTumor-infiltrating lymphocytes are associated with prognosis of ICC patients after complete surgery. CD3+ and CD8+ infiltrate is associated with higher survival and lower recurrence risk, while Foxp3+ infiltrate is associated with worse prognosis. CD3+ infiltrate allows refining prediction of prognosis in early tumors.