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Breast Cancer Research
Published in: Breast Cancer Research 1/2011

Open Access 01-02-2011 | Research article

α-Tocopheryloxyacetic acid: a novel chemotherapeutic that stimulates the antitumor immune response

Authors: Tobias Hahn, Bhumasamudram Jagadish, Eugene A Mash, Kendra Garrison, Emmanuel T Akporiaye

Published in: Breast Cancer Research | Issue 1/2011

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Abstract

Introduction

α-Tocopheryloxyacetic acid (α-TEA) is a novel ether derivative of α-tocopherol that has generated interest as a chemotherapeutic agent because of its selective toxicity toward tumor cells and its ability to suppress tumor growth in various rodent and human xenograft models. We previously reported that oral α-TEA inhibited the growth of both a transplanted (4T1) and a spontaneous MMTV-PyMT mouse model of breast cancer.

Methods

Because little is known about the possible immunological mechanisms underlying the in vivo α-TEA effects, we evaluated the impact of α-TEA therapy on the immune response by characterizing immune cell populations infiltrating the tumor site.

Results

α-TEA treatment resulted in higher frequencies of activated T cells in the tumor microenvironment and twofold and sixfold higher ratios of CD4+ and CD8+ T cells to regulatory T cells, respectively. This finding was correlated with an increased ability of tumor-draining lymph node cells and splenocytes from α-TEA-treated mice to secrete interferon (IFN)-γ in response to CD3 or to mediate a cytolytic response in a tumor-specific fashion, respectively. That the α-TEA-mediated antitumor effect had a T cell-dependent component was demonstrated by the partial abrogation of tumor suppression when CD4+ and CD8+ T cells were depleted. We also determined the intratumoral cytokine and chemokine profile and found that α-TEA treatment increased intratumoral IFN-γ levels but decreased interleukin (IL)-4 levels, suggesting a shift toward a TH1 response. In addition, α-TEA induced higher levels of the inflammatory cytokine IL-6 and the chemokine CCL5.

Conclusions

Taken together, these data suggest that α-TEA treatment, in addition to its direct cytotoxic effects, enhanced the anti-tumor immune response. This study provides a better understanding of the mechanisms of action of α-TEA and its effect on the immune system and may prove useful in designing immune-stimulating strategies to boost the antitumor effects of α-TEA in breast cancer patients.
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Metadata
Title
α-Tocopheryloxyacetic acid: a novel chemotherapeutic that stimulates the antitumor immune response
Authors
Tobias Hahn
Bhumasamudram Jagadish
Eugene A Mash
Kendra Garrison
Emmanuel T Akporiaye
Publication date
01-02-2011
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2011
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2808

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