Abstract：
BACKGROUND:The potential utility of dendritic cells (DC) as cancer vaccines has been established in early trials in human cancers. The concomitant administration of cytotoxic agents and DC vaccines has been previously avoided due to potential immune suppression by chemotherapeutics. Recent studies show that common chemotherapy agents positively influence adaptive and innate anti-tumour immune responses. RESULTS:We investigated the effects of paclitaxel on human DC biology in vitro. DCs appear to sustain a significant level of resistance to paclitaxel and maintain normal viability at concentrations of up to 100 micromol. In some cases this resistance against paclitaxel is significantly better than the level seen in tumour cell lines. Paclitaxel exposure led to a dose dependent increase in HLA class II expression equivalent to exposure to lipopolysaccharide (LPS), and a corresponding increase in proliferation of allogeneic T cells at the clinically relevant doses of paclitaxel. Increase in HLA-Class II expression induced by paclitaxel was not blocked by anti TLR-4 antibody. However, paclitaxel exposure reduced the endocytic capacity of DC but reduced the expression of key pro-inflammatory cytokines such as IL-12 and TNFalpha. Key morphological changes occurred when immature DC were cultured with 100 micromol paclitaxel. They became small rounded cells with stable microtubules, whereas there were little effects on LPS-matured DC. CONCLUSIONS:The effect of paclitaxel on human monocyte derived DC is complex, but in the clinical context of patients receiving preloaded and matured DC vaccines, its immunostimulatory potential and resistance to direct cytotoxicity by paclitaxel would indicate potential advantages to co-administration with vaccines.
journal_name
BMC Immunoljournal_title
BMC immunologyauthors
John J,Ismail M,Riley C,Askham J,Morgan R,Melcher A,Pandha Hdoi
10.1186/1471-2172-11-14subject
Has Abstractpub_date
2010-03-19 00:00:00pages
14issn
1471-2172pii
1471-2172-11-14journal_volume
11pub_type
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