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. 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

Ilaria Marigo  1 , Erika Bosio, Samantha Solito, Circe Mesa, Audry Fernandez, Luigi Dolcetti, Stefano Ugel, Nada Sonda, Silvio Bicciato, Erika Falisi, Fiorella Calabrese, Giuseppe Basso, Paola Zanovello, Emanuele Cozzi, Susanna Mandruzzato, Vincenzo Bronte
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Free article

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

Ilaria Marigo et al. Immunity. .
Free article

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.

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