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

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)-gamma. 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.

Journal

Title: Nature Medicine

Abbreviated Title: Nat Med

Publisher: Springer Science and Business Media LLC

ISSN (Print): 1078-8956

ISSN (Electronic): 1546-170X

Publication date Created: May 2003

Publication date (Electronic): April 21 2003

Publication date (Print): May 2003

Volume: 9

Issue: 5

Pages: 562-567

Article

DOI: 10.1038/nm863

PubMed ID: 12704383

SO-VID: bb16689e-8a2c-4032-bbba-12a55fe264d8

Copyright statement: © 2003

License:

http://www.springer.com/tdm

Product

Self URI (article page): http://www.nature.com/articles/nm863

Self URI (pdf): http://www.nature.com/articles/nm863.pdf

Self URI (pdf): http://www.nature.com/articles/nm863.pdf