Feeding dendritic cells with tumor antigens: self-service buffet or a la carte?

Adoptive transfer of autologous dendritic cells (DC) presenting tumor-assoc iated antigens initiate and sustain an immune response which eradicate muri ne malignancies. Based on these observations, several clinical trials are i n progress testing safety and efficacy with encouraging preliminary reports . In these approaches, ex vivo incubation of DC with a source of tumor anti gens is required to load the relevant antigenic epitopes on the adequate an tigen presenting molecules. Recent data show that in some instances exogeno us DC artificially injected into malignant tissue or endogenous DC attracte d to the tumor nodule by means of gene transfer of GM-CSF and CD40L into ma lignant cells result in efficacious antitumor immunity. In the case of intr atumoral injection of DC the procedure is curative only if DC had been gene tically engineered to produce IL-12, IL-6 or to express CD40L. Evidence has been obtained showing that intratumoral DC can capture and process tumor a ntigens to be presented to T-lymphocytes. Although the exact mechanisms of tumor antigen acquisition by DC are still unclear, available data suggest a role for heat shock proteins released from dying malignant cells and for t he internalization of tumor-derived apoptotic bodies. Roles for tumer necro sis versus apoptosis are discussed in light of the 'danger theory'.