Tumor-associated B7-H1 Promotes T-cell Apoptosis: A Potential Mechanism of Immune Evasion

Nat Med. 2002 Aug;8(8):793-800. doi: 10.1038/nm730. Epub 2002 Jun 24.

Abstract

B7-H1, a recently described member of the B7 family of costimulatory molecules, is thought to be involved in the regulation of cellular and humoral immune responses through the PD-1 receptor on activated T and B cells. We report here that, except for cells of the macrophage lineage, normal human tissues do not express B7-H1. In contrast, B7-H1 is abundant in human carcinomas of lung, ovary and colon and in melanomas. The pro-inflammatory cytokine interferon-gamma upregulates B7-H1 on the surface of tumor cell lines. Cancer cell-associated B7-H1 increases apoptosis of antigen-specific human T-cell clones in vitro, and the apoptotic effect of B7-H1 is mediated largely by one or more receptors other than PD-1. In addition, expression of B7-H1 on mouse P815 tumor increases apoptosis of activated tumor-reactive T cells and promotes the growth of highly immunogenic B7-1(+) tumors in vivo. These findings have implications for the design of T cell-based cancer immunotherapy.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Surface / metabolism
  • Antineoplastic Agents / metabolism
  • Apoptosis Regulatory Proteins
  • Apoptosis*
  • B7-1 Antigen / immunology
  • B7-1 Antigen / metabolism*
  • B7-H1 Antigen
  • Blood Proteins*
  • Cell Separation
  • Fas Ligand Protein
  • Female
  • Flow Cytometry
  • Humans
  • Lymphocyte Activation
  • Melanoma / immunology
  • Melanoma / metabolism
  • Melanoma / pathology
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred Strains
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Peptides*
  • Programmed Cell Death 1 Receptor
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / physiology*
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Cells, Cultured
  • Tumor Escape*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Surface
  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • B7-1 Antigen
  • B7-H1 Antigen
  • Blood Proteins
  • CD274 protein, human
  • Cd274 protein, mouse
  • FASLG protein, human
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • PDCD1 protein, human
  • Pdcd1 protein, mouse
  • Peptides
  • Programmed Cell Death 1 Receptor
  • Recombinant Fusion Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tnfsf10 protein, mouse
  • Tumor Necrosis Factor-alpha