Dendritic Cells Containing Apoptotic Melanoma Cells Prime

Dendritic cells (DCs) phagocytose apoptotic influenza-infected monocytes and cross-present influenza antigen to CD8 T cells, generating a specific CTL response. We investigated whether apoptotic melanoma cells, presented by this mechanism, can lead to CTL responses to tumorassociated antigens and melanoma cells. Apoptotic HLA-A2 MEL-397 melanoma cells were internalized by HLA-A2 immature monocytederived DCs but failed to induce maturation of DCs. When exposed to interleukin 6, interleukin 1b, tumor necrosis factor a, and prostaglandin E2, DCs containing apoptotic MEL-397 cell material matured normally [cross-presenting DCs (cp-DCs)]. Autologous CD8 CTL lines generated with cp-DCs produced tumor necrosis factor when stimulated with HLAA2-binding immunodominant peptides from MelanA/MART1 and MAGE-3 (expressed by MEL-397 cells) but not tyrosinase (absent in MEL-397). T2 target cells loaded with the respective peptides were lysed by these cell lines, although to a lesser extent than by CTL lines generated in the presence of mature DCs and peptides from melanoma-associated antigens. In contrast, lines generated with cp-DCs lysed HLA-A2 MEL526 melanoma cells or allogenic HLA-A2 cp-DCs efficiently, whereas the CTL generated with DCs and peptides had little lytic activity. Mature DCs containing apoptotic tumor cells may thus represent an alternative approach for the therapy of malignant tumors.