CD25 and indoleamine 2,3-dioxygenase are up-regulated by prostaglandin E2 and expressed by...

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CD25 and indoleamine 2,3-dioxygenase are up- regulated by prostaglandin E2 and expressed by tumor-associated dendritic cells in vivo: additional mechanisms of T-cell inhibition by Michael S. von Bergwelt-Baildon, Alexey Popov, Tomo Saric, Jens Chemnitz, Sabine Classen, Marc S. Stoffel, Francesca Fiore, Udo Roth, Marc Beyer, Svenja Debey, Claudia Wickenhauser, Franz-Georg Hanisch, and Joachim L. Schultze Blood Volume 108(1):228-237 July 1, 2006 ©2006 by American Society of Hematology

Transcript of CD25 and indoleamine 2,3-dioxygenase are up-regulated by prostaglandin E2 and expressed by...

Page 1: CD25 and indoleamine 2,3-dioxygenase are up-regulated by prostaglandin E2 and expressed by tumor-associated dendritic cells in vivo: additional mechanisms.

CD25 and indoleamine 2,3-dioxygenase are up-regulated by prostaglandin E2 and expressed by tumor-associated dendritic cells in vivo: additional mechanisms of T-cell

inhibition

by Michael S. von Bergwelt-Baildon, Alexey Popov, Tomo Saric, Jens Chemnitz, Sabine Classen, Marc S. Stoffel, Francesca Fiore, Udo Roth, Marc Beyer, Svenja Debey, Claudia Wickenhauser, Franz-Georg Hanisch, and Joachim L. Schultze

BloodVolume 108(1):228-237

July 1, 2006

©2006 by American Society of Hematology

Page 2: CD25 and indoleamine 2,3-dioxygenase are up-regulated by prostaglandin E2 and expressed by tumor-associated dendritic cells in vivo: additional mechanisms.

Addition of PGE2 to maturing DCs changes their morphology and IL12 production.

Michael S. von Bergwelt-Baildon et al. Blood 2006;108:228-237

©2006 by American Society of Hematology

Page 3: CD25 and indoleamine 2,3-dioxygenase are up-regulated by prostaglandin E2 and expressed by tumor-associated dendritic cells in vivo: additional mechanisms.

Induction of CD25 in monocyte-derived DCs. (A) Analysis of cell-surface expression of CD25 by the different DC populations using flow cytometry.

Michael S. von Bergwelt-Baildon et al. Blood 2006;108:228-237

©2006 by American Society of Hematology

Page 4: CD25 and indoleamine 2,3-dioxygenase are up-regulated by prostaglandin E2 and expressed by tumor-associated dendritic cells in vivo: additional mechanisms.

Induction of CD25 in BDCA-1+ myeloid DCs. (A) Flow cytometry was performed after 18 hours of culture to assess cell-surface expression of CD1c, CD83, CD25 (x-axis), and HLA-DR (y-axis).

Michael S. von Bergwelt-Baildon et al. Blood 2006;108:228-237

©2006 by American Society of Hematology

Page 5: CD25 and indoleamine 2,3-dioxygenase are up-regulated by prostaglandin E2 and expressed by tumor-associated dendritic cells in vivo: additional mechanisms.

Expression and function of IDO in monocyte-derived DCs and myeloid BDCA-1+ DCs. mRNA for RT-PCR and cell lysates for immunoblot analysis were obtained from monocytes, imDCs, or

maDCs cultured in the presence or absence of PGE2.

Michael S. von Bergwelt-Baildon et al. Blood 2006;108:228-237

©2006 by American Society of Hematology

Page 6: CD25 and indoleamine 2,3-dioxygenase are up-regulated by prostaglandin E2 and expressed by tumor-associated dendritic cells in vivo: additional mechanisms.

Monocyte-derived DCs retain the expression of functional IDO and CD25 after removal of PGE2 and maturation signals.

Michael S. von Bergwelt-Baildon et al. Blood 2006;108:228-237

©2006 by American Society of Hematology

Page 7: CD25 and indoleamine 2,3-dioxygenase are up-regulated by prostaglandin E2 and expressed by tumor-associated dendritic cells in vivo: additional mechanisms.

Influence of DC supernatants on T-cell proliferation.

Michael S. von Bergwelt-Baildon et al. Blood 2006;108:228-237

©2006 by American Society of Hematology

Page 8: CD25 and indoleamine 2,3-dioxygenase are up-regulated by prostaglandin E2 and expressed by tumor-associated dendritic cells in vivo: additional mechanisms.

Expression of CD25 and IDO in peritumoral dendritic cells.

Michael S. von Bergwelt-Baildon et al. Blood 2006;108:228-237

©2006 by American Society of Hematology