B7-H1 up-regulation on dendritic-like leukemia cells suppresses T cell immune function through modulation of IL-10/IL-12 production and generation of Treg cells
Abstract
Dendritic-like leukemia cells (DLLC) originating from leukemic cells could potentially induce a T cell-mediated anti-leukemia immune response. It has been demonstrated that B7-H1, a newly identified homologue of CD80/CD86, is abundant in human carcinomas and dendritic cells (DC), can exert co-stimulatory and immune regulatory functions. We demonstrated that B7-H1 was significantly expressed on AML cells and was strongly enhanced after differentiation to DLLC. Blockade of B7-H1 expressed on DLLC results in increased T cell proliferation and Th1 cytokine production, and decreased Th2 cytokine production. Importantly, autologous CTLs induced by DLLC treated with B7-H1 mAb showed significantly increased specific cytotoxcity against AML blasts. We further demonstrated that a significant decrease in IL-12 production, increase in IL-10 production by DLLC, and an increased CD4(+)CD25(+)Foxp3(+) T regulatory population lead to the defective T cell immune response that is induced by B7-H1 up-regulation on DLLC. Our data suggest that up-regulated B7-H1 on DLLC acts as a strong inhibitor of anti-leukemia T cell response, and that blockade of B7-H1 can improve DLLC-mediated anti-leukemia immunity.
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RNA-seq increases accuracy for low-abundance transcripts compared with microarrays.
“It increases accuracy for low-abundance transcripts [44], has a higher resolution for identifying tissue-specific expression and distinguishes expression profiles of closely related paralogues better than microarray-derived profiles [45].”
From Gene co-expression analysis for functional classification and gene–disease predictions (2017) · cites this paper as [44]
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- Authors
- Ge, W., Ma, X., Li, X., Wang, Y., Li, C., Meng, H., Liu, X., Yu, Z., You, S., & Qiu, L.
- Affiliations
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Corresponding author
- Qiu, Lugui
- Venue
- Leukemia Research
- Publisher
- Elsevier BV
- Published
- 2009-07
- Volume
- 33
- Issue
- 7
- Pages
- 948-957
- ISSN
- 0145-2126 (ISSN-L)
- OpenAlex
- W2091084085
- Cited by
- 44
- References
- 37
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 5 · 2020: 1 · 2019: 6 · 2018: 4 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 2 · 2012: 4
- FWCI
- 1.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Leukemia Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- PD-L1, acute myeloid leukemia, T cell response, IL-10, IL-12, regulatory T cells, Foxp3, CTL cytotoxicity, Th1/Th2 cytokines, immune checkpoint blockade, leukemia immunotherapy
- MeSH terms
- Dendritic Cells, Flow Cytometry, Humans, Lymphocyte Activation, Tumor Cells, Cultured, Leukemia, Myeloid, Acute, Antigens, CD, Up-Regulation, Cytokines, Interleukin-10, Apoptosis, Interleukin-12, T-Lymphocytes, Regulatory, B7-H1 Antigen
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