Tumor-induced tolerance and immune suppression depend on the C/EBPbeta transcription factor.
Immunity, 2010/6/25;32(6):790-802.
Marigo I[1], Bosio E, Solito S, Mesa C, Fernandez A, Dolcetti L, Ugel S, Sonda N, Bicciato S, Falisi E, Calabrese F, Basso G, Zanovello P, Cozzi E, Mandruzzato S, Bronte V
Affiliations
PMID: 20605485DOI: 10.1016/j.immuni.2010.05.010
Impact factor: 43.474
Abstract
Tumor growth is associated with a profound alteration in myelopoiesis, leading to recruitment of immunosuppressive cells known as myeloid-derived suppressor cells (MDSCs). We showed that among factors produced by various experimental tumors, the cytokines GM-CSF, G-CSF, and IL-6 allowed a rapid generation of MDSCs from precursors present in mouse and human bone marrow (BM). BM-MDSCs induced by GM-CSF+IL-6 possessed the highest tolerogenic activity, as revealed by the ability to impair the priming of CD8(+) T cells and allow long term acceptance of pancreatic islet allografts. Cytokines inducing MDSCs acted on a common molecular pathway and the immunoregulatory activity of both tumor-induced and BM-derived MDSCs was entirely dependent on the C/EBPbeta transcription factor. Adoptive transfer of tumor antigen-specific CD8(+) T lymphocytes resulted in therapy of established tumors only in mice lacking C/EBPbeta in the myeloid compartment, suggesting that C/EBPbeta is a critical regulator of the immunosuppressive environment created by growing cancers.
MeSH terms
Adoptive Transfer; Animals; Bone Marrow Cells; CCAAT-Enhancer-Binding Protein-beta; Cell Separation; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immune Tolerance; Interleukin-6; Mice; Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; Tumor Escape
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