Abstract Book 2010 - CIMT Annual Meeting

098 Trad | Tumor biology & interaction with the immune system
Tumor infiltrating CD11c+ dendritic cells suppress T cell
activation
Malika Trad 1 , Jennifer Fraszczak 1 , Daniela Lakomy 1 , Maxime Samson 1 , Sylvain Audia 1 ,
Julien Vinit 1 , Emmanuel Katsanis 2 , Nicolas Larmonier 2 * and Bernard Bonnotte 1
1 CR INSERM 866, Université de Bourgogne, Dijon, France
2 Department of Pediatrics, Steele Children’s Research Center, University of Arizona, Tucson, USA
* Equal contribution
Many tumors, including breast cancers are infil-
trated by dendritic cells (DC), known primarily for
their capability to induce and sustain anti-tumoral
immune responses. However, a significant deficit
in the function of DC has been reported in cancer
patients and in various animal tumor models,
which may account for tumor escape from the
immune system. Using the murine breast cancer
model 4T1, we have investigated the phenotypical
and functional characteristics of tumor-infiltrating
DC (TIDC). Our results indicate that TIDC, isolated
from 4T1 tumor-bearing Balb/c mice based on the
expression of the marker CD11c, exhibit a mixed
phenotype associating the expression of mature DC
markers (co-stimulatory molecules) and the Gr-1
molecule (a marker of immunosuppressive myeloid
cells). Functionally, TIDC were unable to induce
allogeneic T cell proliferation and produced low
amount of the pro-inflammatory cytokine IL-12,
required for the T cell activation. Conversely, TIDC
secreted the immunosuppressive cytokine IL-10
and were capable of suppressing the proliferation
of T lymphocytes induced with anti-CD3 and anti-
CD28. The mechanism(s) underlying T cell suppression
by TIDC did not depend on nitric oxide,
but may involve the enzyme indoleamine 2,3-dioxygenase
(IDO) which was significantly upregulated
in these cells.
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