Abstract:
:The liver represents a major and frequently sole site of metastases for many types of cancer, particularly gastrointestinal cancers. We showed previously that coadministration of an engineered hepatic-targeting Listeria monocytogenes (LM) with a cancer vaccine enhanced the antitumor effect of vaccine-induced T cells selectively against hepatic metastases. Here, we show that administration of multiple doses of LM, in the absence of vaccine, generates therapeutic responses against hepatic metastases. LM treatment of mice bearing hepatic metastases induced tumor-specific CD8+ T-cell responses that were enhanced by depletion of regulatory T (Treg) cells by either anti-CD25 or cyclophosphamide treatment. Antitumor activity of LM further depended on natural killer (NK) cell activation but was inhibited by presence of a subset of NK T cells. These results show the utility of LM in the treatment of hepatic metastases even in the absence of vaccine administration and further suggest that blockade of Treg cells and NK T cells will enhance antitumor activity.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Yoshimura K,Laird LS,Chia CY,Meckel KF,Slansky JE,Thompson JM,Jain A,Pardoll DM,Schulick RDdoi
10.1158/0008-5472.CAN-07-0573subject
Has Abstractpub_date
2007-10-15 00:00:00pages
10058-66issue
20eissn
0008-5472issn
1538-7445pii
67/20/10058journal_volume
67pub_type
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