The role of regulatory T cells in the control of natural killer cells: relevance during tumor progression
- 7 November 2006
- journal article
- review article
- Published by Wiley in Immunological Reviews
- Vol. 214 (1), 229-238
- https://doi.org/10.1111/j.1600-065x.2006.00445.x
Abstract
Tumor immunosurveillance relies on cognate immune effectors [lymphocytes and interferon-gamma (IFN-gamma)] and innate immunity [natural killer (NK) cells, natural killer group 2, member D (NKG2D) ligands, perforin/granzyme, and tumor necrosis factor-related apoptosis-inducing ligand]. In parallel, tumor cells promote the expansion of CD4(+)CD25(+) regulatory T cells (Tregs) that counteract T-cell-based anti-tumor immunity. Moreover, accumulating evidence points to a critical role for Tregs in dampening NK cell immune responses. This review summarizes the findings showing that Tregs suppress NK cell effector functions in vitro and in vivo, i.e. homeostatic proliferation, cytotoxicity, and interleukin-12-mediated IFN-gamma production. The molecular mechanism involve selective expression of membrane-bound transforming growth factor-beta on Tregs, which downregulate NKG2D expression on NK cells in vitro and in vivo. The regulatory events dictating NK cell suppression by Tregs have been studied and are discussed. The pathological relevance of the Treg-NK cell interaction has been brought up in tumor models and in patients with cancer. Consequently, inhibition of Tregs through pharmacological interventions should be considered during NK-cell-based immunotherapy of cancer.Keywords
This publication has 82 references indexed in Scilit:
- A Novel Primary Immunodeficiency with Specific Natural-Killer Cell Deficiency Maps to the Centromeric Region of Chromosome 8American Journal of Human Genetics, 2006
- FASL –844C polymorphism is associated with increased activation-induced T cell death and risk of cervical cancerThe Journal of Experimental Medicine, 2005
- A proportion of patients with lymphoma may harbor mutations of the perforin geneBlood, 2005
- Inhibition of CD4+25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamideBlood, 2005
- Amino Acid Requirements for Formation of the TGF-β-Latent TGF-β Binding Protein ComplexesJournal of Molecular Biology, 2005
- CD4+CD25+ regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curativeEuropean Journal of Immunology, 2004
- Cancer immunoediting: from immunosurveillance to tumor escapeNature Immunology, 2002
- Pharmacology of imatinib (STI571)European Journal Of Cancer, 2002
- Efficacy and Safety of Imatinib Mesylate in Advanced Gastrointestinal Stromal TumorsNew England Journal of Medicine, 2002
- Natural killer cells wear different hats: effector cells of innate resistance and regulatory cells of adaptive immunity and of hematopoiesisSeminars in Immunology, 1995