Séminaires du CRC d`Avril 2013

Séminaires du CRC d'Avril 2013
Sauf indications, les séminaires du Centre de Recherche des Cordeliers ont lieu au 15 rue de l’Ecole de Médecine, Paris
75006, à 12h à l'amphithéatre Bilski Pasquier
Vendredi 5 Avril
Chantal BOULANGER
Cardiovascular Research Center - HEGP INSERM - U970
Endothelial microparticles, a new signature of endothelial activation
Microparticles (MPs) are submicron membrane vesicles released in extracellular space following cell activation or apoptosis.
They harbour at their surface most of the membrane-associated proteins of the cells they stem from and are characterized by
the loss of plasma membrane asymmetry resulting in the exposure of phosphatidylserine on their outer leaflet MPs of different
cellular origin circulate in the blood of healthy subjects and although MPs originating from endothelial cells represent a small
population of plasma MPs, their levels increase in cardiovascular diseases. In addition, MPs emerge as important new
biological effectors: they are capable of transferring biological information (proteins, lipids, nucleic acids) from the parent cell to
remote targets, therefore influencing disease progression and repair mechanisms.
Invitée par François Alhenc-Gelas
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Vendredi 19 Avril
Jitka FUCIKOVA
Institut d’Immunology, Prague, République Tchèque
Immunogenic cell death and it´s application in immunotherapeutic protocols.
Treatment of tumors by protocols based on combination of surgery, radiotherapy and systemic chemotherapy resulted in the
improved prognosis of many human cancers. Despite the continuous introduction of new drugs and further improvements of
chemotherapy protocols, it´s likely that at some point chemotherapy will reach its limits and clinical efficacy will plateau.
Immunotherapy has emerged as another treatment modality with the potential to contribute to further improvements in the
survival. The products of advanced cellular terapies must be generated using GMP-approved reagents and number of studies
have addressed the need to generate large numbers of DCs for clinical trials according to regulatory authorities and to current
legislation. The rising knowledge about dendritic cells (DCs) in the immune response against tumors and the ability to prepaire
DCs in vitro leaded to the establishment of immunotherapy protocols. Breakthrough studies that identified markers of
immunogenic tumor cell death after chemotherapy treatment challenge the long-time perception of chemotherapy and
immunotherapy as opposing and incompatible treatment modalities.
Immunogenic cell death is characterized by the early surface exposure of chaperones including calreticulin and HSPs, which
affect dendritic cell (DC) maturation and the uptake and presentation of tumor antigens. It has also been shown that it is
characterized by the late release of high mobility group box 1 (HMGB1), which acts through Toll-like receptor 4 (TLR4) and
augments the presentation of antigens from dying tumor cells to DCs. Most of the data on immunogenic tumor cell death were
obtained using mouse models. In our study, we investigated the capacity of clinically used chemotherapeutics to induce
immunogenic cell death in human tumor cell lines and primary tumor cells. We found that only anthracyclines induced a rapid
translocation of calreticulin, HSP70, and HSP90 to the cell surface and the release of HMGB1 12 hours after the treatment.
The interaction of immature DCs with immunogenic tumor cells led to an increased tumor cell uptake and induces moderate
phenotypic maturation of DCs. Killed tumor cell–loaded DCs efficiently stimulated tumor-specific IFN-g–producing T cells. DCs
pulsed with killed immunogenic tumor cells also induced significantly lower numbers of regulatory T cells than those pulsed
with nonimmunogenic tumor cells. These data indicate that human prostate cancer, ovarian cancer, and acute lymphoblastic
leukemia cells share the key features of immunogenic cell death with mice tumor cells. These data also identify anthracyclines
as anticancer drugs capable of inducing immunogenic cell death in sensitive human tumor cells.
Invitée par Isabelle Cremer
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Vendredi 26 Avril
Barbara DEMENEIX
Professeur au Muséum et Directrice du Laboratoire « Evolution des régulations endocriniennes (CNRS/MNHN) »,
récompensée par le magazine Nature pour son implication auprès de jeunes chercheurs
Thyroid hormone signalling in the neural stem cell niche
We have recently shown that thyroid hormone (T3) and its TRa1 receptor are directly involved in maintaining the balance of
stem cells, transit amplifying cells and migrating neuroblasts in the subventricular zone neural stem cell niche. /In vivo/ gain
and loss of function experiments demonstrate that T_3 /TRa1 favors committment by directly repressing /Sox2 /expression.
Given first, the links between thyroid hormone and metabolic status, and second, the links between metabolic status and stem
cell biology, we are now investigating whether the effects of T3 on neural stem cell committment could implicate metabolic
controls.
Invitée par Catherine Sautès-Fridman