Role des cellules dendritiques dans l'immunite innee antitumorale: Vers de potentielles applications therapeutiques en hematologie

It is arguably admitted that antigen specific, MHC class I restricted-cytotoxic T lymphocytes are key effectors in antitumor immune responses in vivo. Preclinical studies and pioneering clinical trials demonstrated the feasability of host immunization using antiqen pulsed-dendritic cells associated with enhanced CTL precursor frequency in peripheral blood and control of residual tumor growth. Immunoselection such as Ag loss or MHC class I loss variants have been documented in the natural course of melanoma or following such immunotherapies, stressing the need for alternative effector cell therapies. NK cells could be valuable candidates and may be relevant in class I negative tumor models. We are bringing up evidence that resting NK cells can be directly activated by DC following a cell-cell contact, independant of IL-12 and type I IFN in vitro and that this DC/NK cell cross-talk is relevant in innate antitumor immune responses in vivo. These data point to a critical role of DC at the interface between innate and cognate immunity and support implementation of adoptive cell therapy with DC and/or NK cells in haematological malignancies.