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

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 previous...

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Autores principales: Hahn, Tobias, Jagadish, Bhumasamudram, Mash, Eugene A, Garrison, Kendra, Akporiaye, Emmanuel T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109570/
https://www.ncbi.nlm.nih.gov/pubmed/21232138
http://dx.doi.org/10.1186/bcr2808
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author Hahn, Tobias
Jagadish, Bhumasamudram
Mash, Eugene A
Garrison, Kendra
Akporiaye, Emmanuel T
author_facet Hahn, Tobias
Jagadish, Bhumasamudram
Mash, Eugene A
Garrison, Kendra
Akporiaye, Emmanuel T
author_sort Hahn, Tobias
collection PubMed
description 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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spelling pubmed-31095702011-06-08 α-Tocopheryloxyacetic acid: a novel chemotherapeutic that stimulates the antitumor immune response Hahn, Tobias Jagadish, Bhumasamudram Mash, Eugene A Garrison, Kendra Akporiaye, Emmanuel T Breast Cancer Res Research Article 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. BioMed Central 2011 2011-01-13 /pmc/articles/PMC3109570/ /pubmed/21232138 http://dx.doi.org/10.1186/bcr2808 Text en Copyright ©2011 Hahn et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Hahn, Tobias
Jagadish, Bhumasamudram
Mash, Eugene A
Garrison, Kendra
Akporiaye, Emmanuel T
α-Tocopheryloxyacetic acid: a novel chemotherapeutic that stimulates the antitumor immune response
title α-Tocopheryloxyacetic acid: a novel chemotherapeutic that stimulates the antitumor immune response
title_full α-Tocopheryloxyacetic acid: a novel chemotherapeutic that stimulates the antitumor immune response
title_fullStr α-Tocopheryloxyacetic acid: a novel chemotherapeutic that stimulates the antitumor immune response
title_full_unstemmed α-Tocopheryloxyacetic acid: a novel chemotherapeutic that stimulates the antitumor immune response
title_short α-Tocopheryloxyacetic acid: a novel chemotherapeutic that stimulates the antitumor immune response
title_sort α-tocopheryloxyacetic acid: a novel chemotherapeutic that stimulates the antitumor immune response
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109570/
https://www.ncbi.nlm.nih.gov/pubmed/21232138
http://dx.doi.org/10.1186/bcr2808
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