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B7-H1 on myeloid-derived suppressor cells in immune suppression by a mouse model of ovarian cancer.

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.
AuthorsYu Liu, Bin Zeng, Zhuohan Zhang, Yuan Zhang, Rongcun Yang
JournalClinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 129 Issue 3 Pg. 471-81 (Dec 2008) ISSN: 1521-7035 [Electronic] United States
PMID18790673 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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
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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