Live attenuated Listeria monocytogenes effectively treats hepatic colorectal cancer metastases and is strongly enhanced by depletion of regulatory t cells

Kiyoshi Yoshimura, Lindsay S. Laird, Christina Y. Chia, Kristen F. Meckel, Jill E. Slansky, John M. Thompson, Ajay Jain, Drew M. Pardoll, Richard D. Schulick

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)10058-10066
Number of pages9
JournalCancer Research
Volume67
Issue number20
DOIs
StatePublished - Oct 15 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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