Journal
IMMUNITY
Volume 32, Issue 6, Pages 790-802Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2010.05.010
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Funding
- Italian Ministry of Health
- Fondazione Cassa di Risparmio di Padova e Rovigo
- Italian Association for Cancer Research (AIRC)
- Fondazione Italiana Sclerosi Multipla (FISM) [RSF/2005/R/5]
- Association for International Cancer Research (AICR) [08-0518]
- Istituto Superiore Sanita-Alleanza Contro il Cancro [ACC8]
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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/EBP beta transcription factor. Adoptive transfer of tumor antigen-specific CD8(+) T lymphocytes resulted in therapy of established tumors only in mice lacking C/EBP beta in the myeloid compartment, suggesting that C/EBP beta is a critical regulator of the immunosuppressive environment created by growing cancers.
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