Evaluation of a preclinical immunotherapy protocol and of the therapeutic potential of microglia in the treatment of brain tumors
Despite the particular immune status of the central nervous system (CNS), active immunotherapy represents a promising approach for the treatment of malignant brain tumor. Of myeloid origin, microglia are the major immunocompetent cells of the CNS. They harbour an interesting potential in anti-cancer therapies through their preferential location in cerebral tumors and their antigen presenting cell (APC) activities. In order to better characterization of microglia, we have set up an original protocol, based on the mice body irradiation (except the head), allowing to exclude the involvement of migrating peripheral APC. Results showed that resident microglia cross-present in vivo exogenous Ag and prime naive CD8+ T lymphocytes. Moreover, their Ag cross-presentation activity is potentiated by a multistep activation process, including proinflammatory signals (CpG-ODN and GM-CSF) and sCD40L. At the same time, we evaluated immunotherapy for the treatment of mice brain tumor, based on CpG-ODN injection, a potent APC activator, and regulatory T cells (Treg) depletion, which are described to favour tumor escape. Results showed that applied-protocol allows the tumor rejection in all mice and that NK cells are essential for tumor rejection.