Fig. 1.

Proposed mechanisms of action of IFN-DC-based therapies in follicular lymphoma. Intranodal therapy is based on the sequential injection of rituximab and unloaded IFN-DC into the affected lymph node (left side), which results in the enhancement of tumor apoptosis through synergistic mechanisms. Rituximab induces complement and NK-mediated antibody cytotoxicity (CDC and ADCC) of CD20-expressing FL cells and mediates FcR binding and uptake by IFN-DC. IFN-DC enhance NK cell activation and supposedly kill lymphoma cells directly. The local uptake of lymphoma-associated antigens by IFN-DC promote the presentation of tumor antigens from lymphoma cells to specific CD4 and CD8 T cells, resulting in endogenous vaccination and the migration of the T cells to distant lymphoma nodes. Vaccine formulations based on the use of a highly immunogenic tumor cell preparations loaded onto IFN-DC are suitable for all FL patients, especially those without affected superficial targetable nodes (right side). IFN-DC are preventively loaded with autologous lymphoma cells in vitro before their injection in FL patients as a personalized vaccine to induce anti-lymphoma response