Overexpression of B7-H4 in tumor infiltrated dendritic cells

J Immunoassay Immunochem. 2011;32(4):353-64. doi: 10.1080/15321819.2011.578190.

Abstract

DCs infiltrated tumors appears to be phenotypically and functionally defective. B7-H4 was highlighted for its inhibitory role in T cell responses. In this study, we showed that B7-H4 was moderately expressed in imDCs, and up-regulated by IL-10, and TNF-α could counteract the up-regulatory effects of IL-10 on expression of B7-H4 in DCs in vitro. Furthermore, tumor infiltrated DCs expressed B7-H4 at high levels. Blockade of B7-H4 expressed in DCs highly resulted in enhanced T cell proliferation and IFN-γ production significantly. Otherwise, the high level of IL-10 and TNF-α was both detected in the tumor, which suggested that TNF-α can not antagonize the effects of IL-10 on expression of B7-H4 in DCs in vivo. These data indicate that tumor environment may condition local DCs to become dysfunctional in the phenotype, and that the high expression of B7-H4 may contribute to the tumor infiltrated DCs to mediate immune invasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-1 Antigen / genetics
  • B7-1 Antigen / metabolism*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Disease Models, Animal*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Tumor Escape*
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1

Substances

  • B7-1 Antigen
  • Tumor Necrosis Factor-alpha
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1
  • VTCN1 protein, human
  • Interleukin-10
  • Interferon-gamma