Abstract:
:Malignant ascitis (MA) is a highly intractable and immunotherapy-resistant state of advanced gastrointestinal and ovarian cancers. Using a murine model of MA with CT26 colon cancer cells, we here determined that the imbalance between the VEGF-A/vascular permeability factor and its decoy receptor, soluble fms-like tryrosine kinase receptor-1 (sFLT-1), was a major cause of MA resistance to dendritic cell (DC)-based immunotherapy. We found that the ratio of VEGF-A/sFLT-1 was increased not only in murine but also in human MA, and F-gene-deleted recombinant Sendai virus (rSeV/dF)-mediated secretion of human sFLT-1 by DCs augmented not only the activity of DCs themselves, but also dramatically improved the survival of tumor-bearing animals associated with enhanced CTL activity and its infiltration to peritoneal tumors. These findings were not seen in immunodeficient mice, indicating that a VEGF-A/sFLT-1 imbalance is critical for determining the antitumor immune response by DC-vaccination therapy against MA.
journal_name
Mol Cancer Therjournal_title
Molecular cancer therapeuticsauthors
Sugiyama M,Kakeji Y,Tsujitani S,Harada Y,Onimaru M,Yoshida K,Tanaka S,Emi Y,Morita M,Morodomi Y,Hasegawa M,Maehara Y,Yonemitsu Ydoi
10.1158/1535-7163.MCT-10-0479subject
Has Abstractpub_date
2011-03-01 00:00:00pages
540-9issue
3eissn
1535-7163issn
1538-8514pii
1535-7163.MCT-10-0479journal_volume
10pub_type
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