Keynote Conference - Interevent

Symp#9 Immune Cell Biology
Chair Wilson Savino
Wilson Savino
Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil
Introductory notes and talk
Immunological and Clinical Outcomes of a New DC-Based Vaccine
Flavio Salazar-Onfray and Mercedes López
1 Millennium Nucleus on Immunology and Immunotherapy, Faculty of Medicine, University of Chile.
We developed an original method for production of therapeutic dendritic-like cells named Tumor Antigen Presenting
Cells (TAPCells ® ) using an allogeneic melanoma-derived cell lysate (TRIMEL) as activation factor and antigen provider.
TAPCells-based immunotherapy induced T cell-mediated immune responses and improved long-term survival of stage
IV patients in studies involving more than 100 individuals (López et al. 2009, J Clin Oncol; Aguilera et al. 2011, Clin
Cancer Res). Importantly, 61% of tested patients (58 out of 94) showed a Delayed Type Hypersensitivity (DTH) reaction
against TRIMEL indicating the development of anti-tumor immunological memory that correlates with prolonged
patient survival. The in vitro analysis of TRIMEL showed that it contains damage associated molecular patterns such as
HMBG-1 protein, induced by heat shock, capable to improve, through TLR4, the DC maturation and antigen crosspresentation.
In fact, a TLR4 polymorphism correlates with patient clinical outcome. DTH response against TRIMEL was
associated with prolonged survival of the stage IV responder melanoma patients (DTH +; 35 months) compared to the
non-responders (DTH -; 11 months). Furthermore, we observed that DC-vaccination resulted in a three-fold augment
of Th1 cell population releasing IFN-γ and a two-fold increase of Th17 lymphocyte population capable to produce IL-17
in the PBL of DTH+ patients respect to DTH- ones. Antibodies against melanoma antigens can be detected in the sera
from several vaccinated patients, althougth no correlation with clinical responses could be established. Taken
together, our results indicate that TAPCells immunization resulted in two different pattern of response associated to
the immunological and clinical outcome. Our study may contribute to the better understanding of clinical
immunological responses produced by DC-vaccines and to the development of improved DC-based vaccines.
Supported by Fondecyt 1090238 and 1090243.
Eph/ephrin-mediated Interactions Govern Functional Maturation of Developing Thymocytes in the Thymic Epitelial
3D Network
Agustín G Zapata 1 , Juan J Muñoz 2 , David Alfaro 1 , Javier Gª Ceca 1 , Teresa Cejalvo 2 , Esther Trobajas 1 , Sara Montero 1
(1) Department of Cell Biology, Faculty of Biology, (2) Centre for Cytometry and Fluorescence Microscopy,
Complutense University, 28040 Madrid, Spain
The thymus is a primary lymphoid organ in which a 3D epithelial network supports the functional maturation of
lymphoid progenitors into T lymphocytes. The process is highly dependent on the migration of developing thymocytes
to the adequate thymic niche in which thymic epithelial cell (TEC)-thymocyte interactions are critical. In the current
presentation we report the role played in these processes by Eph and ephrins, a large family of receptors and ligands,
respectively involved in the organogenenesis and homeostasis of numerous tisssues, regulating cellular
attachment/detachment. They are extensively expressed in the thymus, partially govern colonization of lymphoid
progenitors and their migration throughout thymic parenchyma and their lack deeply affects not only T-cell maturation
but also correct organization of thymic epithelial network, reflecting the relevance of these molecules in the
thymocyte-TEC interactions that largely modulate the biology of thymus
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