Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity

Tyler J. Curiel, Shuang Wei, Haidong Dong, Xavier Alvarez, Pui Cheng, Peter Mottram, Roman Krzysiek, Keith L. Knutson, Ben Daniel, Maria Carla Zimmermann, Odile David, Matthew Burow, Alan Gordon, Nina Dhurandhar, Leann Myers, Ruth Berggren, Akseli Hemminki, Ronald D. Alvarez, Dominique Emilie, David T. CurielLieping Chen, Weiping Zou

Research output: Contribution to journalArticle

854 Scopus citations

Abstract

Suppression of dendritic cell function in cancer patients is thought to contribute to the inhibition of immune responses and disease progression. Molecular mechanisms of this suppression remain elusive, however. Here, we show that a fraction of blood monocyte-derived myeloid dendritic cells (MDCs) express B7-H1, a member of the B7 family, on the cell surface. B7-H1 could be further upregulated by tumor environmental factors. Consistent with this finding, virtually all MDCs isolated from the tissues or draining lymph nodes of ovarian carcinomas express B7-H1. Blockade of B7-H1 enhanced MDC-mediated T-cell activation and was accompanied by downregulation of T-cell interleukin (IL)-10 and upregulation of IL-2 and interferon (IFN)-γ. T cells conditioned with the B7-H1-blocked MDCs had a more potent ability to inhibit autologous human ovarian carcinoma growth in non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. Therefore, upregulation of B7-H1 +on MDCs in the tumor microenvironment downregulates T-cell immunity. Blockade of B7-H1 represents one approach for cancer immunotherapy.

Original languageEnglish (US)
Pages (from-to)562-567
Number of pages6
JournalNature Medicine
Volume9
Issue number5
DOIs
StatePublished - May 1 2003

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Curiel, T. J., Wei, S., Dong, H., Alvarez, X., Cheng, P., Mottram, P., Krzysiek, R., Knutson, K. L., Daniel, B., Zimmermann, M. C., David, O., Burow, M., Gordon, A., Dhurandhar, N., Myers, L., Berggren, R., Hemminki, A., Alvarez, R. D., Emilie, D., ... Zou, W. (2003). Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nature Medicine, 9(5), 562-567. https://doi.org/10.1038/nm863