L'immunité antitumorale : des concepts à l'immunothérapie active spécifique.

Abstract

Le developpement d' une reponse immunitaire naturelle dirigee contre les tumeurs in vivo ou induite a des fins therapeutiques repose sur le postulat qu' il existe des structures specifiques a la surface des cellules tumorales (l' antigene tumoral) capables d' etre presentees de maniere efficace aux effecteurs du systeme immunitaire (lymphocytes T CD4, CD8 ou natural killer). Les progres realises ces dernieres annees ont montre que les antigenes associes aux tumeurs etaient des variations de differentes proteines du soi. Les cellules dendritiques de l' environnement tumoral jouent un role fondamental dans la presentation de ces antigenes associes aux tumeurs qui met en jeu une panoplie de cytokines immunostimulantes et de molecules de co-stimulation necessaires a la mise en route et au maintien des effecteurs lymphocytaires. Plus recemment, un compartiment vesiculaire secrete par les cellules dendritiques, les exosomes, a ete mis en evidence. Il contient les differentes molecules necessaires a la presentation de l' antigene et peut interagir a distance du site tumoral avec le systeme immunitaire. La comprehension de l' ensemble des mecanismes de l' immunite antitumorale devrait permettre le developpement de strategies therapeutiques efficaces et de comprendre les mecanismes varies developpes par les tumeurs pour echapper au systeme immunitaire.

The field of immunotherapy moved forward with the recent advances in the cell biology of antigen presentation and molecular approaches to tumor antigen characterization. Whereas tumor cells were believed to be poor immunogens, a variety of tumor antigens have been recently characterized that are mostly self-Ag and the question comes: how to overcome self tolerance in cancer bearing patients? Single or string beads CTL defined epitope-based strategies proved useful for immunization in a variety of mouse tumor models and in human melanoma, along with adjuvants such as cytokines or dendritic cells. While the ultimate aim of immunotherapy is to induce lytic effector cells, optimal approaches should not only promote CTL priming but also potent auxiliary response. Recombinant tumor cells or dendritic cells and their exosomes as well as engineered viruses have been demonstrated to elicit specific antitumor immune responses leading to tumor growth suppression and long lasting immunity. Flt3Lis an in vivo DC growth factor that offers novel options in the field of immunization. These immunotherapeutic approaches are being tested in clinical trials, evaluated with novel tools of immunomonitoring and open up novel avenues for disease free patients with poor prognosis factors. Innate immunity might modulate cognate immune responses allowing significant clinical regressions.