The increase of circulating PD-L1-expressing CD68(+) macrophage in ovarian cancer

Tumour Biol. 2016 Apr;37(4):5031-7. doi: 10.1007/s13277-015-4066-y. Epub 2015 Nov 6.

Abstract

Tumor-associated macrophages (TAMs) have been characterized as a critical population of immunosuppressive cells in a variety of tumor types. PD-L1 (also termed B7-H1) has been described to exert co-inhibitory and immune regulatory functions. Here, in ovarian cancer, PD-L1 is selectively overexpressed on some TAM compared that of benign ovarian disease. When expanding the data in peripheral blood, the proportion of PD-L1(+)CD68(+) cell among CD68(+) cells and the intensity of PD-L1 staining on CD68(+) cell in healthy group were similar to that observed in ovarian cyst group; instead, these two measures were significantly higher in ovarian cancer group, thereafter related to TNM stage. Interestingly, intracellular levels of IL-10, IL-6, TNF-α, and IFN-γ in PD-L1(+)CD68(+) macrophage were higher than those in PD-L1(-)CD68(+) macrophage, especially IL-6 expression. Based on the PD-L1 receptor PD-1 expression on tumor-infiltrating cytotoxic cells, our data supported that expression of PD-L1 on TAM promoted apoptosis of T cells via interaction with PD-1 on CD8(+)T cells. Taken together, these results suggested that PD-L1-expressing macrophage represents a novel suppressor cell population in ovarian cancer, which contributes immune escape of ovarian cancer.

Keywords: Immune escape; Ovarian carcinoma; PD-L1; Tumor-associated macrophages.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / genetics*
  • Antigens, Differentiation, Myelomonocytic / genetics*
  • Apoptosis / genetics
  • B7-H1 Antigen / biosynthesis*
  • B7-H1 Antigen / genetics
  • CD8-Positive T-Lymphocytes / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interferon-gamma / genetics
  • Interleukin-10 / genetics
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / genetics
  • Macrophages / metabolism
  • Macrophages / pathology
  • Middle Aged
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / pathology
  • Programmed Cell Death 1 Receptor / biosynthesis*
  • Programmed Cell Death 1 Receptor / genetics
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • B7-H1 Antigen
  • CD274 protein, human
  • CD68 antigen, human
  • IL10 protein, human
  • IL6 protein, human
  • Interleukin-6
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma