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

Anticancer Res. 2017 Jan;37(1):183-190. doi: 10.21873/anticanres.11304.

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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / immunology*
  • Antigens, Differentiation, Myelomonocytic / immunology*
  • Bile Duct Neoplasms / drug therapy
  • Bile Duct Neoplasms / immunology*
  • Bile Duct Neoplasms / pathology
  • Bile Duct Neoplasms / surgery
  • Bile Ducts, Extrahepatic / immunology
  • Bile Ducts, Extrahepatic / pathology
  • Bile Ducts, Extrahepatic / surgery
  • CD8-Positive T-Lymphocytes / immunology*
  • Chemotherapy, Adjuvant
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Macrophages / immunology*
  • Male
  • Middle Aged
  • Prognosis
  • Receptors, Cell Surface / immunology*

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • Receptors, Cell Surface