After phagocytosis of debris from their environment, DCs process this material into peptides that are presented on the cell surface, via major histocompatibility complex (MHC) molecules, for recognition by developing T cells. The interaction between the DCs and T cells induces a cytotoxic immune response against cells displaying this peptide–MHC complex. Likewise, synthetic peptides derived from tumor cells can be presented by DCs to generate an antitumor response. Such synthetic-peptide-based vaccine strategies depend on the laborious identification of tumor-specific antigens and are limited by an individual’s specific set of MHC genes. More recent work has shown that DCs that have phagocytosed apoptotic tumor cells can also induce antitumor immunity.

Furthering this approach, Jim Xiang and colleagues at the University of Saskatchewan (Saskatoon, Saskatchewan), the University of Ottawa (Ottawa, Ontario), and Queen’s University (Kingston, Ontario) compared the antitumor immunity generated by DCs that had been incubated with apoptotic tumor cells (DC/apop) to the effects produced from DC incubation with a synthetic tumor-specific peptide (DC/pept) (Int. J. Cancer 2001, 93, 539–548). When mice were vaccinated with DC/apop and challenged with tumor cell injection, all were able to clear the tumors. DC/pept was less effective at vaccinating against the tumors, with mice bearing an average of 16 pulmonary metastases. As a control, mice vaccinated with immature DCs had more than 200 metastases.

To understand the phenotypic differences between DC/apop and DC/pept, the scientists demonstrated that phagocytosis of apoptotic cells enhanced the maturation of DCs. These matured cells exhibited increased migration toward the site of T lymphocyte stimulation when compared to DC/pept in both in vitro and in vivo chemotaxis assays. Similarly, DC/apop displayed more effective T cell stimulation than DC/pept.

Xiang says that next they will test the therapeutic efficiency of this approach on established tumors.