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

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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/EBPβ transcription factor. Adoptive transfer of tumor antigen-specific CD8+ T lymphocytes resulted in therapy of established tumors only in mice lacking C/EBPβ in the myeloid compartment, suggesting that C/EBPβ is a critical regulator of the immunosuppressive environment created by growing cancers. © 2010 Elsevier Inc.

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Marigo, I., Bosio, E., Solito, S., Mesa, C., Fernandez, A., Dolcetti, L., … Bronte, V. (2010). Tumor-induced tolerance and immune suppression depend on the C/EBPβ transcription factor. Immunity, 32(6), 790–802. https://doi.org/10.1016/j.immuni.2010.05.010

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