TY - JOUR
T1 - Tumor-induced tolerance and immune suppression depend on the C/EBPβ transcription factor
AU - Marigo, Ilaria
AU - Bosio, Erika
AU - Solito, Samantha
AU - Mesa, Circe
AU - Fernandez, Audry
AU - Dolcetti, Luigi
AU - Ugel, Stefano
AU - Sonda, Nada
AU - Bicciato, Silvio
AU - Falisi, Erika
AU - Calabrese, Fiorella
AU - Basso, Giuseppe
AU - Zanovello, Paola
AU - Cozzi, Emanuele
AU - Mandruzzato, Susanna
AU - Bronte, Vincenzo
PY - 2010/6
Y1 - 2010/6
N2 - 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.
AB - 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.
KW - CELLIMMUNO
KW - MOLIMMUNO
UR - http://www.scopus.com/inward/record.url?scp=77953914366&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953914366&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2010.05.010
DO - 10.1016/j.immuni.2010.05.010
M3 - Article
C2 - 20605485
AN - SCOPUS:77953914366
VL - 32
SP - 790
EP - 802
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 6
ER -