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...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Alan M. Kleinfeld [verfasserIn] Clifford Okada [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2005

Schlagwörter:	unbound free fatty acid free fatty acid release immunotherapy

Übergeordnetes Werk:	In: Journal of Lipid Research - Elsevier, 2021, 46(2005), 9, Seite 1983-1990
Übergeordnetes Werk:	volume:46 ; year:2005 ; number:9 ; pages:1983-1990

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1194/jlr.M500151-JLR200

Katalog-ID:	DOAJ062444190

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allfieldsSound	10.1194/jlr.M500151-JLR200 doi (DE-627)DOAJ062444190 (DE-599)DOAJb09be6796e9a4977b6f2452856c2c454 DE-627 ger DE-627 rakwb eng QD415-436 Alan M. Kleinfeld verfasserin aut Free fatty acid release from human breast cancer tissue inhibits cytotoxic T-lymphocyte-mediated killing 2005 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. unbound free fatty acid free fatty acid release immunotherapy Biochemistry Clifford Okada verfasserin aut In Journal of Lipid Research Elsevier, 2021 46(2005), 9, Seite 1983-1990 (DE-627)26601593X (DE-600)1466675-3 15397262 nnns volume:46 year:2005 number:9 pages:1983-1990 https://doi.org/10.1194/jlr.M500151-JLR200 kostenfrei https://doaj.org/article/b09be6796e9a4977b6f2452856c2c454 kostenfrei http://www.sciencedirect.com/science/article/pii/S002222752032945X kostenfrei https://doaj.org/toc/0022-2275 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_252 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2006 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 46 2005 9 1983-1990
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author	Alan M. Kleinfeld
spellingShingle	Alan M. Kleinfeld misc QD415-436 misc unbound free fatty acid misc free fatty acid release misc immunotherapy misc Biochemistry Free fatty acid release from human breast cancer tissue inhibits cytotoxic T-lymphocyte-mediated killing
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topic_title	QD415-436 Free fatty acid release from human breast cancer tissue inhibits cytotoxic T-lymphocyte-mediated killing unbound free fatty acid free fatty acid release immunotherapy
topic	misc QD415-436 misc unbound free fatty acid misc free fatty acid release misc immunotherapy misc Biochemistry
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title	Free fatty acid release from human breast cancer tissue inhibits cytotoxic T-lymphocyte-mediated killing
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title_full	Free fatty acid release from human breast cancer tissue inhibits cytotoxic T-lymphocyte-mediated killing
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title_sort	free fatty acid release from human breast cancer tissue inhibits cytotoxic t-lymphocyte-mediated killing
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title_auth	Free fatty acid release from human breast cancer tissue inhibits cytotoxic T-lymphocyte-mediated killing
abstract	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.
abstractGer	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.
abstract_unstemmed	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.
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title_short	Free fatty acid release from human breast cancer tissue inhibits cytotoxic T-lymphocyte-mediated killing
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