Indoleamine 2,3-dioxygenase contributes to tumor cell evasion of T cell-mediated rejection.
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.
Friberg
Maria
M
Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA.
Jennings
Ronald
R
Alsarraj
Marwan
M
Dessureault
Sophie
S
Cantor
Alan
A
Extermann
Martine
M
Mellor
Andrew L
AL
Munn
David H
DH
Antonia
Scott J
SJ
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D005434:Flow Cytometry; D007108:Immune Tolerance; D007167:Immunotherapy; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma / Q000032:analysis; D008198:Lymph Nodes / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009369:Neoplasms / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000494:pharmacology; D014366:Tryptophan Oxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; C028129:tryptophan methyl ester; D007371:Interferon-gamma; D014364:Tryptophan; D014366:Tryptophan Oxygenase