Human activated T lymphocytes modulate IDO expression in tumors through Th1/Th2 balance.
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.
Godin-Ethier
Jessica
J
Research Centre, Centre Hospitalier de l'Université de Montréal-Hôpital Notre-Dame, Université de Montréal and Institut du Cancer de Montréal, Montreal, Quebec, Canada.
Pelletier
Sandy
S
Hanafi
Laïla-Aïcha
LA
Gannon
Philippe O
PO
Forget
Marie-Andrée
MA
Routy
Jean-Pierre
JP
Boulassel
Mohamed-Rachid
MR
Krzemien
Urszula
U
Tanguay
Simon
S
Lattouf
Jean-Baptiste
JB
Arbour
Nathalie
N
Lapointe
Réjean
R
D001943:Breast Neoplasms / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology; D018920:Coculture Techniques; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D007371:Interferon-gamma / Q000378:metabolism / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D014407:Tumor Cells, Cultured
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma