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

Ilaria Marigo, Erika Bosio, Samantha Solito, Circe Mesa, Audry Fernandez, Luigi Dolcetti, Stefano Ugel, Nada Sonda, Silvio Bicciato, Erika Falisi, Fiorella Calabrese, Giuseppe Basso, Paola Zanovello, Emanuele Cozzi, Susanna Mandruzzato, Vincenzo Bronte

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)790-802
Number of pages13
JournalImmunity
Volume32
Issue number6
DOIs
Publication statusPublished - Jun 2010

Keywords

  • CELLIMMUNO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Infectious Diseases

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