Prognostic impact of tumour-infiltrating immune cells on biliary tract cancer

Abstract

Background:Biliary tract cancers (BTC) are relatively rare malignant tumours with poor prognosis. It is known from other solid neoplasms that antitumour inflammatory response has an impact on tumour behaviour and patient outcome. The aim of this study was to provide a comprehensive characterisation of antitumour inflammatory response in human BTC.Methods:Tumour-infiltrating T lymphocytes (CD4+, CD8+, and Foxp3+), natural killer cells (perforin+), B lymphocytes (CD20+), macrophages (CD68+) as well as mast cells (CD117+) were assessed by immunohistochemistry in 375 BTC including extrahepatic (ECC; n=157), intrahepatic (ICC; n=149), and gallbladder (GBAC; n=69) adenocarcinomas. Overall and intraepithelial quantity of tumour-infiltrating immune cells was analysed. Data were correlated with clinicopathological variables and patient survival.Results:The most prevalent inflammatory cell type in BTC was the T lymphocyte. Components of the adaptive immune response decreased, whereas innate immune response components increased significantly in the biliary intraepithelial neoplasia – primary carcinoma – metastasis sequence. BTC patients with intraepithelial tumour-infiltrating CD4+, CD8+, and Foxp3+ T lymphocytes showed a significantly longer overall survival. Number of total intraepithelial tumour-infiltrating Foxp3+ regulatory T lymphocytes (HR: 0.492, P=0.002) and CD4+ T lymphocytes (HR: 0.595, P=0.008) were tumour grade- and UICC-stage-independent prognosticators. The subtype-specific evaluation revealed that the tumour-infiltrating lymphocytic infiltrate is a positive outcome predictor in ECC and GBAC but not in ICC.Conclusion:Our findings characterise the immune response in cholangiocarcinogenesis and identify inflammatory cell types that influence the outcome of BTC patients. Further, we show that BTC subtypes show relevant differences with respect to density, quality of inflammation, and impact on patient survival.

Prognostic Impact of CD163+ Macrophages in Tumor Stroma and CD8+ T-Cells in Cancer Cell Nests in Invasive Extrahepatic Bile Duct Cancer

“…Those findings suggest that immune evasion might allow perineural invasion and low infiltration of CD8 + T-cells, leading to poor survival in patients with perihilar EHBC. In this study, the extent of CD8 + T-cells within cancer cell nests alone was not found to be a significant prognostic indicator as shown by previous studies (15,16). The reason for this is thought to be that we excluded mucosal cancer, which is associated with high frequency of infiltrating CD8 + T-cells and favorable survival (14).…”

“…This finding has also been related to favorable survival in EHBC (15,16). However, the prognostic impact of tumor-infiltrating M2-like macrophages and the relationship of prognosis with CD8 + T-cells are unclear in patients with EHBC.…”

CD8+ T Cells That Coexpress RORγt and T-bet Are Functionally Impaired and Expand in Patients with Distal Bile Duct Cancer

“…In DBDC, CD8 + T cells, CD4 + T cells, CD4 + FOXP3 + regulatory T cells (Tregs) and macrophages infiltrate the tumor tissue. However, most of the T cells are CD8 + T cells, and despite the high level of tumor-infiltrating CD8 + T cells in DBDC patients, the tumor cells often persist and metastasize (3). At present, the lineage-specific phenotype and functional relevance of CD8 + T cells in DBDC has not yet been fully revealed.…”

T cell receptor repertoire profiling predicts the prognosis of HBV‐associated hepatocellular carcinoma

“…It have been demonstrated that infiltrating T lymphocytes are closely associated with tumor development and clinical outcome in various tumor types 8, 9, 10. T cells are selectively activated and undergoing a massive expansion via specific recognition of tumor neoantigens.…”