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 Autoreactivity and Alloreactivity to Cancer (A2C)

Composition of the team

This team is constituted by the reunification of three programs of research mainly devoted to the understanding of the immune system confronted to solid cancer or leukemia. During the last four years, the research programs of each of the partners have been focused on the identification of the cellular mechanisms leading to tumor/leukemia tolerance or rejection by the immune system, through the development of specific experimental models. Recently collected observations led us to formulate the hypothesis of common immune mechanisms leading to tolerance to semi-allogeneic fetuses (alloreactivity) or to tumor cells (autoreactivity). Indeed, we identified a sub-population of regulatory T cells that appears as the central actor in permitting both tumor and fetuses implantation. In parallel, we also identified the mechanism by which regulatory T cells controlled conventional T cells during alloreactive response.
The new team has now the objective to combine the study of autoreactivity and alloreactivity in the field of cancer. The A2C program is split into 4 interactive projects (P1 to P4). The P1 project aims to identify the immunological and molecular signatures associated with (i) early tumor cell and fetus implantation and (ii) resistance to conventional effector T cells. The P2 project will study in depth the interaction between effector T cells, regulatory T cells and antigen presenting cells during alloreactive responses, and the possibility to modulate this response by acting on one or several cellular partners with regard to consequences on anti-tumor response. The P3 project will test in experimental models the possibility to directly eliminate tumor or leukemia by direct infusion of alloreactive T cells, engineered to be eliminated in vivo in case of deleterious effect. The P4 project will assess a polyepitopic genetic vaccination for patients with residual CML.
The originality and strength of the A2C project comes from its use of (i) system immunology approaches - including global T cell receptor repertoire and gene expression analyses, of (ii) in vivo imaging specifically developed to analyze regulatory and effector T cells interaction and (iii) of “humanized mice” and its capacity to translate relevant achievements to clinical evaluation.

Composition of the team

Permanent staff:

Non-permanent staff:
 
 
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