Indoleamine 2,3-dioxygenase contributes to tumor cell evasion of T cell-mediated rejection

Int J Cancer. 2002 Sep 10;101(2):151-5. doi: 10.1002/ijc.10645.


The priming of an appropriate anti-tumor T cell response rarely results in the rejection of established tumors. The characteristics of tumors that allow them to evade a T cell-mediated rejection are unknown for many tumors. We report on evidence that the expression of the immunosuppressive enzyme, indoleamine 2,3-dioxygenase (IDO) by mononuclear cells that invade tumors and tumor-draining lymph nodes, is 1 mechanism that may account for this observation. Lewis lung carcinoma (LLC) cells stimulated a more robust allogeneic T cell response in vitro in the presence of a competitive inhibitor of IDO, 1-methyl tryptophan. When administered in vivo this inhibitor also resulted in delayed LLC tumor growth in syngeneic mice. Our study provides evidence for a novel mechanism whereby tumors evade rejection by the immune system, and suggests the possibility that inhibiting IDO may be developed as an anti-cancer immunotherapeutic strategy.

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Flow Cytometry
  • Immune Tolerance
  • Immunotherapy
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Interferon-gamma / analysis
  • Lymph Nodes / cytology
  • Lymph Nodes / enzymology
  • Lymph Nodes / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neoplasms / enzymology*
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Tryptophan / analogs & derivatives*
  • Tryptophan / pharmacology
  • Tryptophan Oxygenase / antagonists & inhibitors
  • Tryptophan Oxygenase / metabolism*
  • Tumor Cells, Cultured


  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • tryptophan methyl ester
  • Interferon-gamma
  • Tryptophan
  • Tryptophan Oxygenase