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Dead or Alive: Immunogenicity of Human Melanoma Cells When Presented by Dendritic Cells¹

Institute for Cancer Studies, Division of Oncology and Cellular Pathology, University of Sheffield Medical School, Sheffield, S10 2RX [M. S-M., C. M., A. M.], and Department of Ophthalmology and Orthoptics, Royal Hallamshire Hospital, Sheffield, S10 2JF [K. S., I. R.], United Kingdom

Uveal melanoma is an aggressive malignancy with a poor prognosis despite current therapeutic intervention. These tumors have been shown to be antigenic because they express a number of melanoma-associated antigens and are therefore attractive targets for immunotherapy. Here, we investigated the immunogenicity of uveal melanoma cells that have undergone apoptosis and compared this with their necrotic or live counterparts. The fate of the tumor antigens in these cells largely depends on their ability to be processed and phagocytosed by dendritic cells (DCs). Flow cytometric analysis shows that human DCs form conjugates more efficiently with dead uveal melanoma cells, and consequently these are effective stimuli of lymphocyte proliferation. However, only DCs pulsed with apoptotic cells were able to induce proliferation of CD8⁺ cytotoxic T cells and stimulate antigen-specific T cells. This study demonstrates for the first time that DCs derived from melanoma patients process and present antigens derived from both HLA-matched or HLA-mismatched human apoptotic tumor cells stimulating both CD4⁺ and CD8⁺ T cells. This approach may be important to the development of DC-based immunotherapies for melanoma.

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