Abstract
The identification of the most efficient strategy for tumor antigen loading of dendritic cells (DCs) remains a challenge in cancer immunotherapy protocols. Autologous dead tumor cells have been demonstrated to constitute an acceptable source of multiple tumor-associated antigens (TAA) to pulse DCs. However the optimal approach for inducing cell death that would lead to effective endocytosis and activation of DCs remains controversial. In this study we have induced and defined 3 distinct mechanisms of tumor cell death (apoptosis, necrosis and fusion-mediated cell death), and investigated their differential effects on DCs. Bone marrow-derived DCs demonstrated comparable uptake of primary apoptotic, necrotic, or fused dead tumor cells. Furthermore, the distinct modes of cancer cell death had analogous potential in activating the transcription factors NF-κB and STAT1 and in maturing DCs, resulting in an equally effective stimulation of immune T cells. The current study therefore provides further informations on the use of dead whole tumor cells as antigen sources for effective active anti-cancer immunotherapy.
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Supported by grants from the French League against Cancer (National, Burgundy, and Nièvre Committees). N.L. received grants from the French National League against Cancer, and D.C. from the Saône et Loire League against Cancer. E.K. and N.L. received financial support from the NIH R01 grant CA104926.
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Larmonier, N., Mérino, D., Nicolas, A. et al. Apoptotic, necrotic, or fused tumor cells: An equivalent source of antigen for dendritic cell loading. Apoptosis 11, 1513–1524 (2006). https://doi.org/10.1007/s10495-006-8765-0
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DOI: https://doi.org/10.1007/s10495-006-8765-0