Apoptotic, necrotic, or fused tumor cells: An equivalent source of antigen for dendritic cell loading

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-kappaB 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.

Localized Hyperthermia Combined with Intratumoral Dendritic Cells Induces Systemic Antitumor Immunity

“…Additionally, incubation of heat-treated RM-1 cells with immature dendritic cells resulted in induction of CD80 and CCR7 molecules, indicating maturation of dendritic cells. Similar results have been reported with tumor lysates derived from UV-irradiated apoptotic and necrotic tumor cells (34,35). The induction of CCR7 is a hallmark of dendritic cell maturation because CCR7 is the ''homing receptor'' for antigen-loaded dendritic cells to migrate into draining lymph nodes, where they would present the processed antigens to T cells for the induction of adaptive immune response (36)(37)(38).…”

Dendritic Cells Trigger Tumor Cell Death by a Nitric Oxide-Dependent Mechanism

“…However, the optimal approach for inducing cell death that would lead to effective endocytosis and activation of DCs remains controversial (22,25,26). The cytotoxic effect of DCs toward tumor cells was reported to be related to the activation of a caspase-dependent apoptotic pathway (5, 27) through activation of death receptors such as Fas, TNF-␣ receptor, and TRAIL receptor (4,6,28).…”

Peroxynitrite-Dependent Killing of Cancer Cells and Presentation of Released Tumor Antigens by Activated Dendritic Cells

“…We investigated the tumoricidal activity of mouse BMDCs (32), selected based on CD11c expression. Consistent with previous results (6,14,15,19,20), our data indicate that BMDCs were not endowed with inherent cytotoxic activity against B16F10 melanoma cells except for the highest tumor cell/BMDC ratio (1:20) (Fig.…”