The role of regulatory T cells and TH17 cells in multiple myeloma

Clin Dev Immunol. 2012;2012:293479. doi: 10.1155/2012/293479. Epub 2012 Mar 27.

Abstract

The development of multiple myeloma (MM) involves a series of genetic alterations and changes in the bone marrow microenvironment, favoring the growth of the tumor and failure of local immune control. Quantitative and functional alterations in CD4(+) and CD8(+) T cells have been described in MM. The balance between T regulatory cells (Treg) and T helper (Th) 17 cells represents one essential prerequisite for maintaining anti-tumor immunity in MM. Tregs play an important role in the preservation of self-tolerance and modulation of overall immune responses against infections and tumor cells. In MM patients, Tregs seem to contribute to myeloma-related immune dysfunction and targeting them could, therefore, help to restore and enhance vital immune responses. Th17 cells protect against fungal and parasitic infections and participate in inflammatory reactions and autoimmunity. The interplay of TGF-β and IL-6, expressed at high levels in the bone marrow of myeloma patients, may affect generation of Th17 cells both directly or via other pro-inflammatory cytokines and thereby modulate antitumor immune responses. A detailed analysis of the balance between Tregs and Th17 cells seems necessary in order to design more effective and less toxic modes of immunotherapy myeloma which still is an uncurable malignancy.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • Forkhead Transcription Factors / biosynthesis
  • Forkhead Transcription Factors / immunology
  • Humans
  • Immune Tolerance
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / immunology
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / pathology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / pathology
  • Th17 Cells / immunology*
  • Th17 Cells / pathology
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / immunology

Substances

  • Biomarkers, Tumor
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-6
  • Transforming Growth Factor beta