Cited by 1,314Immunotherapy and Immune ResponsesCancer Immunotherapy and BiomarkersT-cell and B-cell Immunology

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

Curiel, Tyler J., Wei, Shuang, Dong, Haidong, Alvarez, Xavier, Cheng, Pui, Mottram, Peter, Krzysiek, Roman, Knutson, Keith L. +14 more·2003·Nature Medicine

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.

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Crossref · 10.1038/nm863

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Authors
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., Curiel, D. T., Chen, L., & Zou, W.
Affiliations
  • Tulane University (US)
  • Mayo Clinic (US)
  • Inserm (FR)
  • University of Washington (US)
  • Baylor University Medical Center (US)
  • University of Alabama (US)
Corresponding author
  • Curiel, Tyler J.
  • Zou, Weiping
Venue
Nature Medicine
Published
2003-04-21
Volume
9
Issue
5
Pages
562-567
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
OpenAlex
W2053353274
Cited by
1,314
References
41
Citations by year
2026: 20 · 2025: 34 · 2024: 60 · 2023: 67 · 2022: 64 · 2021: 77 · 2020: 99 · 2019: 69 · 2018: 65 · 2017: 73 · 2016: 68 · 2015: 83 · 2014: 51 · 2013: 68 · 2012: 47
FWCI
12.91
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Heart, Lung, and Blood Institute (HL67962, R01HL067962)
  • National Cancer Institute (R01CA092562, CA 97085, CA86881, CA 092562, R01CA097085, R01CA086881, P50CA089019, CA8661, CA-89019)
  • National Center for Research Resources (P51RR000164, RR00164.)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
PD-L1, myeloid dendritic cells, monocyte-derived dendritic cells, antitumor immunity, ovarian carcinoma, T cell activation, IL-10, interferon-gamma, tumor microenvironment, cancer immunotherapy, immune checkpoint blockade
MeSH terms
Animals, Blood Proteins, Cytotoxicity, Immunologic, Dendritic Cells, Female, Humans, Lymphocyte Activation, Membrane Glycoproteins, Ovarian Neoplasms, Peptides, T-Lymphocytes, Antigens, CD, Mice, SCID, Mice, Inbred NOD, Interleukin-10, B7-1 Antigen, Interleukin-12, Myeloid Cells, Mice, B7-H1 Antigen

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