Free fatty acid release from human breast cancer tissue inhibits cytotoxic T-lymphocyte-mediated killing
Immune-mediated antitumor activities confront a variety of tumor-mediated defense mechanisms. Here, we describe a new mechanism involving FFA that may allow breast cancer to evade immune clearance. We determined the IC50 at which unbound free fatty acids (FFAu) inhibit murine cytotoxic T-lymphocyte...
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2005-09-01
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Online Access: | http://www.sciencedirect.com/science/article/pii/S002222752032945X |
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doaj-b09be6796e9a4977b6f2452856c2c4542021-04-27T04:43:46ZengElsevierJournal of Lipid Research0022-22752005-09-0146919831990Free fatty acid release from human breast cancer tissue inhibits cytotoxic T-lymphocyte-mediated killingAlan M. Kleinfeld0Clifford Okada1To whom correspondence should be addressed.; Torrey Pines Institute for Molecular Studies, San Diego, CA 92121Torrey Pines Institute for Molecular Studies, San Diego, CA 92121Immune-mediated antitumor activities confront a variety of tumor-mediated defense mechanisms. Here, we describe a new mechanism involving FFA that may allow breast cancer to evade immune clearance. We determined the IC50 at which unbound free fatty acids (FFAu) inhibit murine cytotoxic T-lymphocyte (CTL)-mediated killing to assess the physiologic relevance of this phenomenon. We found that the IC50 for unbound oleate is 125 ± 30 nM, ∼200-fold greater than normal plasma levels. FFA inhibition, however, may play an important role in breast cancer because we found that large quantities of FFAs are released constitutively into the media surrounding samples of human breast cancer but not normal or benign tissue. FFAu concentration ([FFAu]) increased to at least 25 nM in 20 of 22 cancer tissue samples and exceeded 100 nM in 11 patients. Media from these samples inhibited CTL-mediated killing. Extrapolation from our in vitro conditions suggests that for tumor interstitial fluid, in vivo [FFAu] may be 300-fold greater than we observed in vitro.Although breast cancer release of FFA may suppress effector cell antitumor activity, strategies that reduce interstitial [FFAu] may significantly improve antitumor immune therapies.http://www.sciencedirect.com/science/article/pii/S002222752032945Xunbound free fatty acidfree fatty acid releaseimmunotherapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alan M. Kleinfeld Clifford Okada |
spellingShingle |
Alan M. Kleinfeld Clifford Okada Free fatty acid release from human breast cancer tissue inhibits cytotoxic T-lymphocyte-mediated killing Journal of Lipid Research unbound free fatty acid free fatty acid release immunotherapy |
author_facet |
Alan M. Kleinfeld Clifford Okada |
author_sort |
Alan M. Kleinfeld |
title |
Free fatty acid release from human breast cancer tissue inhibits cytotoxic T-lymphocyte-mediated killing |
title_short |
Free fatty acid release from human breast cancer tissue inhibits cytotoxic T-lymphocyte-mediated killing |
title_full |
Free fatty acid release from human breast cancer tissue inhibits cytotoxic T-lymphocyte-mediated killing |
title_fullStr |
Free fatty acid release from human breast cancer tissue inhibits cytotoxic T-lymphocyte-mediated killing |
title_full_unstemmed |
Free fatty acid release from human breast cancer tissue inhibits cytotoxic T-lymphocyte-mediated killing |
title_sort |
free fatty acid release from human breast cancer tissue inhibits cytotoxic t-lymphocyte-mediated killing |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2005-09-01 |
description |
Immune-mediated antitumor activities confront a variety of tumor-mediated defense mechanisms. Here, we describe a new mechanism involving FFA that may allow breast cancer to evade immune clearance. We determined the IC50 at which unbound free fatty acids (FFAu) inhibit murine cytotoxic T-lymphocyte (CTL)-mediated killing to assess the physiologic relevance of this phenomenon. We found that the IC50 for unbound oleate is 125 ± 30 nM, ∼200-fold greater than normal plasma levels. FFA inhibition, however, may play an important role in breast cancer because we found that large quantities of FFAs are released constitutively into the media surrounding samples of human breast cancer but not normal or benign tissue. FFAu concentration ([FFAu]) increased to at least 25 nM in 20 of 22 cancer tissue samples and exceeded 100 nM in 11 patients. Media from these samples inhibited CTL-mediated killing. Extrapolation from our in vitro conditions suggests that for tumor interstitial fluid, in vivo [FFAu] may be 300-fold greater than we observed in vitro.Although breast cancer release of FFA may suppress effector cell antitumor activity, strategies that reduce interstitial [FFAu] may significantly improve antitumor immune therapies. |
topic |
unbound free fatty acid free fatty acid release immunotherapy |
url |
http://www.sciencedirect.com/science/article/pii/S002222752032945X |
work_keys_str_mv |
AT alanmkleinfeld freefattyacidreleasefromhumanbreastcancertissueinhibitscytotoxictlymphocytemediatedkilling AT cliffordokada freefattyacidreleasefromhumanbreastcancertissueinhibitscytotoxictlymphocytemediatedkilling |
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