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Immunity. 2010 Jun 25;32(6):790-802. doi: 10.1016/j.immuni.2010.05.010. Epub 2010 Jun 3.

Tumor-induced tolerance and immune suppression depend on the C/EBPbeta transcription factor.

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1
Department of Oncology and Surgical Sciences, University of Padua, 35128 Padua, Italy.

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.

PMID:
20605485
DOI:
10.1016/j.immuni.2010.05.010
[Indexed for MEDLINE]
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