Drug- and cell-mediated antitumor cytotoxicities modulate cross-presentation of tumor antigens by myeloid dendritic cells
作者:
Alessandra Galetto,
Stefano Buttiglieri,
Sarah Forno,
Francesco Moro,
Antonio Mussa,
Lina Matera,
期刊:
Anti-Cancer Drugs
(OVID Available online 2003)
卷期:
Volume 14,
issue 10
页码: 833-843
ISSN:0959-4973
年代: 2003
出版商: OVID
关键词: antigen presentation/processing;apoptosis;dendritic cell;tumor immunity;vaccination
数据来源: OVID
摘要:
The way a tumor cell dies is believed to influence both its engulfment by dendritic cells (DC) and access of the relevant antigen(s) to the cross-presentation pathway. Here we have studied the effect of lymphokine activated killer (LAK) cells, &ggr;-radiation and the antimetabolite drug 5-fluorouracil (5-FU) on tumor uptake by HLA-matched DC, and DC presentation of tumor antigens to autologous T lymphocytes. LAK cells and radiation were the best inducers of apoptotic death (Annexin-V+/propidium iodide−) on the gastric cell line KATO III and a primary gastric carcinoma, respectively. The highest rate of tumor uptake by monocyte-derived, granulocyte macrophage colony stimulating factor/interleukin (IL)-4-driven DC was associated with 5-FU, followed by radiation. These treatments also induced high levels of heat shock protein (hsp70). In contrast, only DC that had been taken up 5-FU- or LAK-treated tumors up-modulated IL-12 and presented tumor-associated antigens with increased efficiency, as shown by class I MHC-restricted interferon-&ggr; release and cytotoxic responses by autologous lymphocytes. Together, these data indicate that apoptotic death induced by anti-cancer therapies can induce distinct patterns of class I MHC cross-presentation of gastric carcinoma-associated antigens to cytotoxic T lymphocyte precursors.
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