CD169 identifies an anti-tumour macrophage subpopulation in human hepatocellular carcinoma

J Pathol. 2016 Jun;239(2):231-41. doi: 10.1002/path.4720. Epub 2016 Apr 27.

Abstract

Macrophages are a major component of most solid tumours and can exert both anti- and pro-tumourigenic functions. Although the immunosuppressive/pro-tumour roles of macrophages have been widely examined, significantly less is known about macrophage subpopulations that have potential anti-tumour properties in humans. In the present study, a population of CD169(+) macrophages with relatively high expression levels of HLA-DR and CD86 was identified in human hepatocellular carcinoma tissues. The frequency of CD169-expressing macrophages within cancer nests was significantly lower than that found in paired non-tumour areas. In vitro experiments revealed that in the presence of anti-CD3 stimulation, CD169(+) macrophages could significantly enhance the proliferation, cytotoxicity, and cytokine production capacity of CD8(+) T cells in a CD169 molecule-dependent manner. Autocrine TGF-β produced by tumour-stimulated macrophages was involved in the down-regulation of CD169 expression on these cells. Moreover, the accumulation of CD169(+) macrophages in tumour tissues was negatively associated with disease progression and predicted favourable survival in hepatocellular carcinoma patients, which was in contrast to the trend observed for total CD68(+) macrophages. Therefore, CD169 might act as a co-stimulatory molecule for cytotoxic T-cell activation, and could define a population of tumour-infiltrating macrophages with potential anti-tumour properties in human hepatocellular carcinoma tissues. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Keywords: CD169; hepatocellular carcinoma; macrophage; tumour microenvironments.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B7-2 Antigen / immunology
  • B7-2 Antigen / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / pathology
  • Down-Regulation
  • Female
  • HLA-DR Antigens / immunology
  • HLA-DR Antigens / metabolism
  • Humans
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / pathology
  • Lymphocyte Activation
  • Macrophages / immunology*
  • Macrophages / pathology
  • Male
  • Middle Aged
  • Sialic Acid Binding Ig-like Lectin 1 / immunology*
  • Sialic Acid Binding Ig-like Lectin 1 / metabolism
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / pathology
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / metabolism
  • Tumor Microenvironment
  • Young Adult

Substances

  • B7-2 Antigen
  • CD86 protein, human
  • HLA-DR Antigens
  • SIGLEC1 protein, human
  • Sialic Acid Binding Ig-like Lectin 1
  • Transforming Growth Factor beta