Highlights on molecular mechanisms of MDSC-Mediated Immune Suppression: Paving the way for new working hypotheses

Samantha Solito, Laura Pinton, Vera Damuzzo, Susanna Mandruzzato

Research output: Contribution to journalArticle

Abstract

MDSCs have been recognized in the last years as tolerogenic cells, potentially dangerous in the context of neoplasia, since they are able to induce tolerance to a variety of anti-tumor effectors, including CD4 and CD8 T cells. It is currently believed that the origin of MDSCs is due to an arrest of the myeloid differentiation process caused by tumor-secreted factors released in the tumor microenvironment that are able to exert an effect on myeloid progenitors, rendering them unable to terminally differentiate into dendritic cells, granulocytes and macrophages. As a consequence, these immature myeloid cells acquire suppressive activity through the activation of several mechanisms, controlled by different transcription factors. The lack of consensus about the phenotypical characterization of human MDSCs is the result of the existence of different MDSC subsets, most likely depending on the tumor in which they expand and on the tumor specific cytokine cocktail driving their activation. This, in turn, might also influence the mechanisms of MDSC-mediated immune suppression. In this review article we address the role of tumor-derived factors (TDFs) in MDSC-recruitment and activation, discuss the complex heterogeneity of MDSC phenotype and analyze the crosstalk between activated T cells and MDSCs.

Original languageEnglish
Pages (from-to)722-737
Number of pages16
JournalImmunological Investigations
Volume41
Issue number6-7
DOIs
Publication statusPublished - Aug 2012

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Keywords

  • Innate Immunity
  • Myeloid Cells
  • Myeloid Derived Suppressor Cells
  • Tolerance

ASJC Scopus subject areas

  • Immunology

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