Abstract Book 2010 - CIMT Annual Meeting

097 Fraszczak | Tumor biology & interaction with the immune system
Killer dendritic cells inhibit Treg differentiation
Jennifer Fraszczak 1 , Malika Trad 1 , Nona Janikashvili 1,2 , Daniela Lakomy 1 , Maxime Samson
1 , Sylvain Audia 1 , Julien Vinit 1 , Nicolas Larmonier 2 , Bernard Bonnotte 1
1 CR Inserm 866, Faculty of medicine, 7 boulevard Jeanne d’Arc, 21000 Dijon, France
2 Department of Paediatrics, Steele Children's Research Centre, University of Arizona, Tucson, AZ 85724, USA
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Known for decades as the principal messengers of
the immune system, dendritic cells (DC) play a critical
role in the initiation and regulation of immune
responses against tumor. We have recently reported
on the non-conventional direct tumor killing activity
of DC. We have demonstrated that mouse DC generated
from bone marrow precursors are endowed
with the capability to kill multiple types of cancer
cells and have identified peroxynitrites as the main
effector molecules underlying this cytotoxic activity.
Importantly these killer DC (KDC) are capable
of presenting tumor antigens from the cancer cells
they had killed to specific T cells thereby inducing
an efficient antitumor immune response. We here
evaluate whether KDC may modulate regulatory T
cells (Treg), critical contributors of cancer-induced
immune tolerance and major obstacles for tumor
immunotherapy. Our results indicate that KDC significantly
impair the polarization of naive T cells
into FoxP3-expressing immunosuppressive Treg
but foster their differentiation into T bet-expressing
Th-1 cells. The cellular and molecular bases
responsible for this negative modulation of Treg by
KDC is currently under investigation.