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.
Pubmed ID: 20605485 RIS Download
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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