Human activated T lymphocytes modulate IDO expression in tumors through Th1/Th2 balance

J Immunol. 2009 Dec 15;183(12):7752-60. doi: 10.4049/jimmunol.0901004.


Previous cancer vaccination approaches have shown some efficiency in generating measurable immune responses, but they have rarely led to tumor regression. It is therefore possible that tumors emerge with the capacity to down-regulate immune counterparts, through the local production of immunosuppressive molecules, such as IDO. Although it is known that IDO exerts suppressive effects on T cell functions, the mechanisms of IDO regulation in tumor cells remain to be characterized. Here, we demonstrate that activated T cells can induce functional IDO expression in breast and kidney tumor cell lines, and that this is partly attributable to IFN-gamma. Moreover, we found that IL-13, a Th2 cytokine, has a negative modulatory effect on IDO expression. Furthermore, we report IDO expression in the majority of breast and kidney carcinoma samples, with infiltration of activated Th1-polarized T cells in human tumors. These findings demonstrate complex control of immune activity within tumors. Future immune therapeutic interventions should thus include strategies to counteract these negative mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / enzymology
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology
  • Carcinoma, Renal Cell / enzymology
  • Carcinoma, Renal Cell / immunology*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / immunology
  • Coculture Techniques
  • Gene Expression Regulation, Enzymologic / immunology*
  • Humans
  • Immunophenotyping
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / biosynthesis*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / physiology
  • Interferon-gamma / metabolism
  • Interferon-gamma / physiology
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology*
  • Lymphocytes, Tumor-Infiltrating / enzymology
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Th1 Cells / enzymology
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th1 Cells / pathology
  • Th2 Cells / enzymology
  • Th2 Cells / immunology*
  • Th2 Cells / pathology
  • Tumor Cells, Cultured


  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Interferon-gamma