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

Abstract

Aim: The aim of this study was to examine the clinicopathological influence of tumor-infiltrating cluster of differentiation (CD) 163⁺ macrophages and CD8⁺ T-cells, and to clarify the prognostic effects of these cells in patients with invasive extrahepatic bile duct cancer (EHBC).

Materials and methods: The numbers of CD8⁺ T-cells in cancer cell nests and CD163⁺ macrophages in tumor stroma were evaluated using immunohistochemistry in 101 resected EHBC specimens. Correlations with clinicopathological variables and overall survival were analyzed.

Results: Perihilar EHBC and perineural invasion were significantly associated with a low number of tumor-infiltrating CD8⁺ T-cells. Poorly- differentiated histology and nodal metastasis were significantly associated with a high number of tumor-infiltrating CD163⁺ macrophages. A combination of high number of CD8⁺ T-cells and low number of CD163⁺ macrophages was independently related to better overall survival in the whole patient cohort (hazard ratio=0.127, p<0.001) and in patients treated with adjuvant chemotherapy (hazard ratio=0.139, p=0.021).

Conclusion: Infiltrating CD163⁺ macrophages in tumor stroma and CD8⁺ T-cells in cancer cell nests have a prognostic impact in patients with EHBC following resection and also after adjuvant chemotherapy.

Keywords: CD163; CD8; Extrahepatic bile duct cancer; tumor-associated macrophages; tumor-infiltrating lymphocytes.