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.
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Blockade of the B7-H1/PD-1 pathway has been investigated as a therapeutic target in solid human tumors.
“blockade of B7-H1/PD-1 pathway was investigated as therapeutic targets in solid human tumors [9,30]”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [9]
In animal models, introducing B7-1 into tumors or blocking inhibitory B7 family members reduces tumor growth or causes spontaneous tumor rejection.
“Animal model studies have shown that introduction of B7-1 into tumors by transfection or blockade of inhibitory B7 family members can reduce tumor growth or result in spontaneous tumor rejection in vivo [7–13].”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [9]
Exhausted CD8+ T cells have been found in patients with melanoma, ovarian cancer, and hepatocellular carcinoma.
“Exhausted CD8+ T cells were found in patients with melanoma [*31], ovarian cancer [9] and hepatocellular carcinoma (HCC) [30].”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [9]
In the tumor microenvironment, stimulatory and inhibitory B7 family members are imbalanced, with high inhibitory and low stimulatory expression.
“There is an active imbalance between stimulatory and inhibitory B7 family members in the tumor microenvironment [1,3,7,8].”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [9]
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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
- ORCID
- 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
- Licence
- www.springer.com/tdm (tdm)
- 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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