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

Nature Medicine volume 8, pages 793–800 (2002)Cite this article

A Corrigendum to this article was published on 01 September 2002

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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-γ 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.

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Figure 1: B7-H1 expression in normal and cancer tissues.
Figure 2: B7-H1+ 624mel melanoma cells promote apoptosis of tumor-specific M15 CD8+ CTLs and are resistant to growth inhibition by the CTLs.
Figure 3: Human breast carcinoma HBL-100 constitutively expressing B7-H1 promotes apoptosis of the CEA-specific M99 CD8+ CTLs.
Figure 4: Role of FasL and IL-10 in B7-H1-mediated apoptosis of activated T cells.
Figure 5: Expression of B7-H1 on P815 tumor promotes apoptosis of T cells and increases tumor growth in vivo.

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  • 27 August 2002

    Incorrectly stated no declaration in August 2002 issue. Corrigendum run in September 2002 issue. I updated the link in the original article to contain a "yes" declaration including the explanatory text.

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Acknowledgements

This study was supported in part by the US National Institutes of Health grants CA79915 and CA85721 (to L.C.), CA37343 (to V.A.L.), CA80782 and CA82677 (to E.C.) and CA15083 (Mayo Clinic Cancer Center). We thank L. Murphy for the processing of tissue samples; L.L. Hinkley for data processing; Z. Yu for facilitating a study on the expression of B7-H1 on a lung cancer line; H. Kobayashi for advice on T-cell culture; and K. Jensen for editing the manuscript. Some of the results presented in this paper (expression of B7-H1 in human tumor lines) were presented at a National Cancer Institute Symposium, 'Tumor escape from immune recognition: Molecular mechanism and functional significance', 22–23 August 1999, Baltimore, Maryland.

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Authors and Affiliations

  1. Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA

    Haidong Dong, Hideto Tamura, Fumiya Hirano, Dallas B. Flies, Jun Lu, Gefeng Zhu, Koji Tamada, Vanda A. Lennon, Esteban Celis & Lieping Chen

  2. Department of Otorhinolaryngology, Mayo Clinic, Rochester, Minnesota, USA

    Scott E. Strome

  3. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA

    Diva R. Salomao, Patrick C. Roche & Vanda A. Lennon

  4. Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA

    Vanda A. Lennon

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Correspondence to Lieping Chen.

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A patent application regarding the method to enhance immune responses by blockade of B7-H1 was filed before the publication.

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Dong, H., Strome, S., Salomao, D. et al. Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion. Nat Med 8, 793–800 (2002). https://doi.org/10.1038/nm730

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