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

Clin Immunol. 2008 Dec;129(3):471-81. doi: 10.1016/j.clim.2008.07.030. Epub 2008 Sep 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / immunology
  • Antigens, Differentiation / immunology
  • Antigens, Differentiation / metabolism
  • B7-1 Antigen / biosynthesis*
  • B7-1 Antigen / genetics
  • B7-1 Antigen / immunology
  • B7-H1 Antigen
  • CD11b Antigen / biosynthesis
  • CD11b Antigen / immunology
  • CTLA-4 Antigen
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology
  • Immunophenotyping
  • Male
  • Membrane Glycoproteins / biosynthesis*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Cells / immunology
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / immunology*
  • Ovarian Neoplasms / pathology
  • Peptides / genetics
  • Peptides / immunology
  • Programmed Cell Death 1 Receptor
  • RNA, Small Interfering / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Specific Pathogen-Free Organisms
  • Spleen / immunology
  • Transfection


  • 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