TY - JOUR
T1 - Human activated T lymphocytes modulate IDO expression in tumors through Th1/Th2 balance
AU - Godin-Ethier, Jessica
AU - Pelletier, Sandy
AU - Hanafi, Laïla Aïcha
AU - Gannon, Philippe O.
AU - Forget, Marie Andrée
AU - Routy, Jean Pierre
AU - Boulassel, Mohamed Rachid
AU - Krzemien, Urszula
AU - Tanguay, Simon
AU - Lattouf, Jean Baptiste
AU - Arbour, Nathalie
AU - Lapointe, Réjean
PY - 2009/12/15
Y1 - 2009/12/15
N2 - 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-γ. 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.
AB - 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-γ. 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.
UR - http://www.scopus.com/inward/record.url?scp=76249093444&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=76249093444&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.0901004
DO - 10.4049/jimmunol.0901004
M3 - Article
C2 - 19933867
AN - SCOPUS:76249093444
SN - 0022-1767
VL - 183
SP - 7752
EP - 7760
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -