title: Induced and natural regulatory T cells in human cancer.
abstract: BACKGROUND
  Evidence suggests that FOXP3(+)CD25(high)CD4(+) regulatory T cells (Treg) which accumulate in cancer may have beneficial or unfavorable effects on prognosis. The presence in tumor-associated inflammatory infiltrates of two subsets of Treg with distinct phenotypic and functional profiles might explain these conflicting observations.
  
  
  METHODS
  Human inducible (i) Treg arising by tumor-driven conversion of conventional CD4(+) T cells are highly suppressive, therapy-resistant Treg which down-regulate anti-tumor immune responses, promoting tumor growth. Natural (n) Treg, normally responsible for maintaining peripheral tolerance, control cancer-associated inflammation, which favors tumor progression. This division of labor between nTreg and iTreg is not absolute, and overlap may be common. Nevertheless, iTreg play a critical and major role in cancer and cancer therapy. The tumor microenvironment determines the type, frequency and suppression levels of accumulating Treg.
  
  
  CONCLUSIONS
  In cancer, a selective removal or silencing of iTreg and not of nTreg should be a therapeutic goal. However, the implementation of this challenging strategy requires further studies of cellular and molecular crosstalk among immune cells in the tumor microenvironment.
authors: University of Pittsburgh Cancer Institute, Pathology, Hillman Cancer Center, 5117 Centre Ave, Pittsburgh, PA 15213, USA. whitesidetl@upmc.edu
authors: Theresa L
authors: TL
authors: Whiteside
authors: Patrick
authors: P
authors: Schuler
authors: Bastian
authors: B
authors: Schilling
mesh_terms: D006801:Humans; D009369:Neoplasms / Q000276:immunology*; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*