WP5 - Identification of immune cell biomarkers using models of PNS
Leader: R. Liblau (MD, PhD, CPTP UMR1043-CNRS 5282)
An important limitation to understand mechanisms of AE and PNS and to identify specific treatments is the absence of appropriate disease models and the complexity of the immune mechanisms. Indeed, according to the subgroup of AE and PNS and the associated autoantibodies, different aspects of immune/nervous system interactions with different pathophysiological mechanisms seem to be involved. In some cases, there are converging evidence suggesting that neurological symptoms result from a direct role of autoantibodies that block synaptic function of the targeted proteins. The best example is NMDAR-Abs encephalitis. However, in other cases, both cellular and humoral responses probably lead to brain tissue injury and in some cases, such as anti-Yo or anti-Hu PNS, only the cellular immune response could be involved in neuronal death. In this last case, there is no biomarker to follow the immune reaction and the exact immune mechanisms are totally unknown.
In the last years, we developed animal models to study the mechanisms of immune reaction in specific subtypes of PNS. The purpose of this WP is to use these models to identify potential specific B and T cell signature as biomarkers of PNS and to develop new treatment strategies.
Task 5.1: Analysis of HA model for the study of T cell involvement in PCD
Objective: Characterize the T cells modulating the balance between anti-tumor immunity and cerebellar autoimmunity.
Task 5.2: Generation of Yo-PCD model to characterized neoantigens able to induce PCD
Objective: Develop a mouse model of Yo-PCD using tumor lines expressing CDR2 and/or CDR2L to study and validate candidate pathways for initiation of tumor immune surveillance.