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

I Marigo, E Bosio, S Solito, C Mesa, A Fernandez… - Immunity, 2010 - cell.com
I Marigo, E Bosio, S Solito, C Mesa, A Fernandez, L Dolcetti, S Ugel, N Sonda, S Bicciato
Immunity, 2010cell.com
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 …
Summary
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.
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