Abstract |
Myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing hosts and are associated with immune suppression. Here, we described high level of expression of B7-H1 (CD274), PD-1 (CD279) and CTLA4 (CD152) by Gr-1(+)CD11b(+) MDSCs obtained from both ascites and spleens of mice bearing the 1D8 ovarian carcinoma, whereas B7-DC (CD273), CD40 and CD86 were absent. In contrast, B7-H1, PD-1 and CTLA-4 expression was not detected on Gr-1(+)CD11b(+) cells from naive mice. Expression of B7-H1 by Gr-1(+)CD11b(+) cells from naive mice could be induced by co-culture with 1D8 ovarian carcinoma cells. Gr-1(+)CD11b(+) cells derived from 1D8 tumor-bearing mice markedly suppressed antigen-specific immune responses, whereas Gr-1(+)CD11b(+) cells from naive mice did not. siRNA-mediated knockdown of B7-H1 in Gr-1(+)CD11b(+) cells of 1D8 tumor-bearing mice alleviated suppression of antigen-specific immune responses. Suppression of antigen-specific immune responses via B7-H1 on Gr-1(+)CD11b(+) myeloid cells was mediated by CD4(+)CD25(+) Foxp3(+) T regulatory cells and required PD-1. Antibody blockade of either B7-H1 or PD-1 retarded the growth of 1D8 tumor in mice. This suggests that expression of B7-H1 on Gr-1(+)CD11b(+) myeloid cells triggered by the 1D8 mouse model of ovarian carcinoma suppresses antigen-specific immunity via interaction with PD-1 on CD4(+)CD25(+) Foxp3(+) regulatory T cells.
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Authors | Yu Liu, Bin Zeng, Zhuohan Zhang, Yuan Zhang, Rongcun Yang |
Journal | Clinical immunology (Orlando, Fla.)
(Clin Immunol)
Vol. 129
Issue 3
Pg. 471-81
(Dec 2008)
ISSN: 1521-7035 [Electronic] United States |
PMID | 18790673
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, CD
- Antigens, Differentiation
- B7-1 Antigen
- B7-H1 Antigen
- CD11b Antigen
- CTLA-4 Antigen
- Cd274 protein, mouse
- Ctla4 protein, mouse
- Forkhead Transcription Factors
- Foxp3 protein, mouse
- Membrane Glycoproteins
- Pdcd1 protein, mouse
- Peptides
- Programmed Cell Death 1 Receptor
- RNA, Small Interfering
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Topics |
- Animals
- Antigens, CD
(immunology)
- Antigens, Differentiation
(immunology, metabolism)
- B7-1 Antigen
(biosynthesis, genetics, immunology)
- B7-H1 Antigen
- CD11b Antigen
(biosynthesis, immunology)
- CTLA-4 Antigen
- Enzyme-Linked Immunosorbent Assay
- Female
- Flow Cytometry
- Forkhead Transcription Factors
(genetics, immunology)
- Immunophenotyping
- Male
- Membrane Glycoproteins
(biosynthesis, genetics, immunology)
- Mice
- Mice, Inbred C57BL
- Myeloid Cells
(immunology)
- Ovarian Neoplasms
(genetics, immunology, pathology)
- Peptides
(genetics, immunology)
- Programmed Cell Death 1 Receptor
- RNA, Small Interfering
(genetics)
- Reverse Transcriptase Polymerase Chain Reaction
- Signal Transduction
- Specific Pathogen-Free Organisms
- Spleen
(immunology)
- Transfection
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