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

Persistent Link:
http://hdl.handle.net/10150/610114
Title:
alpha-Tocopheryloxyacetic acid: a novel chemotherapeutic that stimulates the antitumor immune response
Author:
Hahn, Tobias; Jagadish, Bhumasamudram; Mash, Eugene; Garrison, Kendra; Akporiaye, Emmanuel
Affiliation:
Robert W Franz Cancer Research Center, Earle A Chiles Research Institute, Providence Portland Medical Center, 4805 NE Glisan Street, Portland, OR 97213, USA; Department of Chemistry and Biochemistry, University of Arizona, 1306 East University Boulevard, Tucson, AZ 85721, USA
Issue Date:
2011
Publisher:
BioMed Central
Citation:
Hahn et al. Breast Cancer Research 2011, 13:R4 http://breast-cancer-research.com/content/13/1/R4
Journal:
Breast Cancer Research
Rights:
© 2011 Hahn et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
INTRODUCTION:alpha-Tocopheryloxyacetic acid (alpha-TEA) is a novel ether derivative of alpha-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 alpha-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 alpha-TEA effects, we evaluated the impact of alpha-TEA therapy on the immune response by characterizing immune cell populations infiltrating the tumor site.RESULTS:alpha-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 alpha-TEA-treated mice to secrete interferon (IFN)-gamma in response to CD3 or to mediate a cytolytic response in a tumor-specific fashion, respectively. That the alpha-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 alpha-TEA treatment increased intratumoral IFN-gamma levels but decreased interleukin (IL)-4 levels, suggesting a shift toward a TH1 response. In addition, alpha-TEA induced higher levels of the inflammatory cytokine IL-6 and the chemokine CCL5.CONCLUSIONS:Taken together, these data suggest that alpha-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 alpha-TEA and its effect on the immune system and may prove useful in designing immune-stimulating strategies to boost the antitumor effects of alpha-TEA in breast cancer patients.
EISSN:
1465-542X
DOI:
10.1186/bcr2808
Version:
Final published version
Additional Links:
http://breast-cancer-research.com/content/13/1/R4

Full metadata record

DC FieldValue Language
dc.contributor.authorHahn, Tobiasen
dc.contributor.authorJagadish, Bhumasamudramen
dc.contributor.authorMash, Eugeneen
dc.contributor.authorGarrison, Kendraen
dc.contributor.authorAkporiaye, Emmanuelen
dc.date.accessioned2016-05-20T08:58:55Z-
dc.date.available2016-05-20T08:58:55Z-
dc.date.issued2011en
dc.identifier.citationHahn et al. Breast Cancer Research 2011, 13:R4 http://breast-cancer-research.com/content/13/1/R4en
dc.identifier.doi10.1186/bcr2808en
dc.identifier.urihttp://hdl.handle.net/10150/610114-
dc.description.abstractINTRODUCTION:alpha-Tocopheryloxyacetic acid (alpha-TEA) is a novel ether derivative of alpha-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 alpha-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 alpha-TEA effects, we evaluated the impact of alpha-TEA therapy on the immune response by characterizing immune cell populations infiltrating the tumor site.RESULTS:alpha-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 alpha-TEA-treated mice to secrete interferon (IFN)-gamma in response to CD3 or to mediate a cytolytic response in a tumor-specific fashion, respectively. That the alpha-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 alpha-TEA treatment increased intratumoral IFN-gamma levels but decreased interleukin (IL)-4 levels, suggesting a shift toward a TH1 response. In addition, alpha-TEA induced higher levels of the inflammatory cytokine IL-6 and the chemokine CCL5.CONCLUSIONS:Taken together, these data suggest that alpha-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 alpha-TEA and its effect on the immune system and may prove useful in designing immune-stimulating strategies to boost the antitumor effects of alpha-TEA in breast cancer patients.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://breast-cancer-research.com/content/13/1/R4en
dc.rights© 2011 Hahn et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)en
dc.titlealpha-Tocopheryloxyacetic acid: a novel chemotherapeutic that stimulates the antitumor immune responseen
dc.typeArticleen
dc.identifier.eissn1465-542Xen
dc.contributor.departmentRobert W Franz Cancer Research Center, Earle A Chiles Research Institute, Providence Portland Medical Center, 4805 NE Glisan Street, Portland, OR 97213, USAen
dc.contributor.departmentDepartment of Chemistry and Biochemistry, University of Arizona, 1306 East University Boulevard, Tucson, AZ 85721, USAen
dc.identifier.journalBreast Cancer Researchen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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