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Live Attenuated Listeria Monocytogenes Effectively Treats Hepatic Colorectal Cancer Metastases and Is Strongly Enhanced by Depletion of Regulatory T Cells
- Source :
- Cancer Research. 67:10058-10066
- Publication Year :
- 2007
- Publisher :
- American Association for Cancer Research (AACR), 2007.
-
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. [Cancer Res 2007;67(20):10058–66]
- Subjects :
- Cancer Research
Colorectal cancer
Vaccines, Attenuated
Cancer Vaccines
T-Lymphocytes, Regulatory
Metastasis
Interferon-gamma
Mice
T-Lymphocyte Subsets
Animals
Medicine
Cyclophosphamide
Mice, Inbred BALB C
business.industry
Liver Neoplasms
Cancer
T lymphocyte
medicine.disease
Listeria monocytogenes
Killer Cells, Natural
Oncology
Immunology
Cancer research
Cancer vaccine
Colorectal Neoplasms
business
Liver cancer
Cell activation
CD8
T-Lymphocytes, Cytotoxic
Subjects
Details
- ISSN :
- 15387445 and 00085472
- Volume :
- 67
- Database :
- OpenAIRE
- Journal :
- Cancer Research
- Accession number :
- edsair.doi.dedup.....318f60305c12ec377f9a255788caca5c