Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion

• Published in: Nature medicine Vol. 8; no. 8; pp. 793 - 800
• Main Authors: Chen, Lieping, Dong, Haidong, Strome, Scott E, Salomao, Diva R, Tamura, Hideto, Hirano, Fumiya, Flies, Dallas B, Roche, Patrick C, Lu, Jun, Zhu, Gefeng, Tamada, Koji, Lennon, Vanda A, Celis, Esteban
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.08.2002
• Subjects: Analysis; Animals; Antibodies, Monoclonal; Antigens, CD; Antigens, Surface - metabolism; Antineoplastic Agents - metabolism; Apoptosis; Apoptosis Regulatory Proteins; B7-1 Antigen - immunology; B7-1 Antigen - metabolism; B7-H1 Antigen; Blood Proteins; Cell Separation; Fas Ligand Protein; Female; Flow Cytometry; Glycoproteins; Humans; Immunotherapy; Lymphocyte Activation; Melanoma - immunology; Melanoma - metabolism; Melanoma - pathology; Membrane Glycoproteins - metabolism; Mice; Mice, Inbred Strains; Neoplasms - immunology; Neoplasms - metabolism; Neoplasms - pathology; Peptides; Physiological aspects; Programmed Cell Death 1 Receptor; Recombinant Fusion Proteins - immunology; Recombinant Fusion Proteins - metabolism; Signal Transduction; T cells; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - physiology; TNF-Related Apoptosis-Inducing Ligand; Tumor Cells, Cultured; Tumor Escape; Tumor Necrosis Factor-alpha - metabolism; Tumors
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm730

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.