Dendritic cell viability is decreased after phagocytosis of apoptotic tumor cells induced by staurosporine or vaccinia virus infection

C. Gandini Bone Marrow Transplantation Unit, Department of Medical Oncology, Istituto Nazionale Tumori, via Venezian 1, 20133 Milan, Italy. dinicola@istitutotumori.mi.it

BACKGROUND AND OBJECTIVES: Dendritic cells (DC) primed with tumor antigens can effectively mediate the regression of a variety of established solid malignancies in both murine and human models. Several experimental studies indicate that apoptotic bodies are an optimal source of tumor antigens for ex vivo priming of DC. However, the clinical use of killed tumor cells as a source of antigens will require an optimal methodology to induce effective tumor cell apoptosis. DESIGN AND METHODS: The goal of this study was to compare the efficiency of three agents for inducing neoplastic B lymphocyte apoptosis; staurosporine, infection by modified vaccinia (MVA) viral particles and ultraviolet C (UVC) radiation. RESULTS: The three methods were finely tuned to induce apoptosis in more than 90% of tumor cells after 24 hours of exposure. However, the viability of monocyte-derived DC, loaded with B-cell tumor apoptotic bodies induced by staurosporine or MVA viral particles, decreased dramatically within 48 hours after phagocytosis of the killed neoplastic cells. The persistence of the apoptosis-inducing agents in the apoptotic bodies and not in the tumor supernatant, was responsible for the observed damage to DC viability. In contrast, DC viability was not affected after uptake of tumor cells killed through UVC-irradiation. Furthermore, B-lymphoblastic cell line (LCL)-specific T cells were reactivated by DC loaded with apoptotic bodies induced by UVC-rays. INTERPRETATION AND CONCLUSIONS: Since the method used to induce tumor cell apoptosis might be detrimental to DC viability, these findings should be considered when designing anticancer vaccination programs.

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