PMID- 34400394
OWN - NLM
STAT- MEDLINE
DCOM- 20220106
LR  - 20220416
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 81
IP  - 20
DP  - 2021 Oct 15
TI  - Dietary Fats High in Linoleic Acids Impair Antitumor T-cell Responses by Inducing 
      E-FABP-Mediated Mitochondrial Dysfunction.
PG  - 5296-5310
LID - 10.1158/0008-5472.CAN-21-0757 [doi]
AB  - The most recent American Dietary Guidelines (2020-2025) recommend shifting 
      dietary fats from solid saturated fats to unsaturated oils. Dietary oils contain 
      different compositions of unsaturated fatty acids (UFA). Oleic acid (OA) and 
      linoleic acid (LA) are the most common UFA in dietary oils. How individual UFA in 
      oils regulate immune cell function and cancer risk remains unclear. Here we 
      demonstrated that high-fat diets (HFD) rich either in OA or LA induced a similar 
      degree of murine obesity, but the LA-rich HFD specifically promoted mammary tumor 
      growth. LA impaired antitumor T-cell responses by promoting naive T-cell 
      apoptosis and inhibiting TNFalpha production. While exogenous OA and LA were taken up 
      by T cells with similar efficacy, only LA induced significant mitochondrial 
      reactive oxygen species production and lipid peroxidation. Importantly, naive T 
      cells predominantly expressed epidermal fatty acid binding protein (E-FABP), 
      which is central in facilitating LA mitochondrial transport and cardiolipin 
      incorporation. Genetic depletion of E-FABP rescued LA-impaired T-cell responses 
      and suppressed LA-rich HFD-associated mammary tumor growth. Collectively, these 
      data suggest that dietary oils high in LA promote mammary tumors by inducing 
      E-FABP-mediated T-cell dysfunction. SIGNIFICANCE: These findings suggest that 
      modulation of dietary oil composition and inhibition of E-FABP activity may 
      represent novel strategies to enhance T-cell function in the prevention and 
      treatment of obesity-associated cancers.
CI  - (c)2021 American Association for Cancer Research.
FAU - Jin, Rong
AU  - Jin R
AD  - Department of Microbiology and Immunology, University of Louisville, Louisville, 
      Kentucky.
AD  - Department of Immunology, School of Basic Medical Sciences, Peking University, 
      Beijing, P.R. China.
FAU - Hao, Jiaqing
AU  - Hao J
AUID- ORCID: 0000-0002-2834-7255
AD  - Department of Microbiology and Immunology, University of Louisville, Louisville, 
      Kentucky.
FAU - Yi, Yanmei
AU  - Yi Y
AD  - Department of Microbiology and Immunology, University of Louisville, Louisville, 
      Kentucky.
AD  - Department of Histology and Embryology, Guangdong Medical University, Zhanjiang, 
      P.R. China.
FAU - Yin, Di
AU  - Yin D
AD  - Department of Microbiology and Immunology, University of Louisville, Louisville, 
      Kentucky.
AD  - School of Basic Medical Sciences, Guangdong Medical University, Guangzhou, P.R. 
      China.
FAU - Hua, Yuan
AU  - Hua Y
AD  - Department of Microbiology and Immunology, University of Louisville, Louisville, 
      Kentucky.
FAU - Li, Xiaohong
AU  - Li X
AD  - Kentucky Biomedical Research Infrastructure Network Bioinformatics Core, 
      Department of Anatomical Sciences and Neurobiology, University of Louisville, 
      Louisville, Kentucky.
FAU - Bao, Hanmei
AU  - Bao H
AD  - Barshop Institute for Longevity and Aging Studies, University of Texas Health 
      Science Center at San Antonio, San Antonio, Texas.
FAU - Han, Xianlin
AU  - Han X
AD  - Barshop Institute for Longevity and Aging Studies, University of Texas Health 
      Science Center at San Antonio, San Antonio, Texas.
AD  - Department of Medicine, University of Texas Health Science Center at San Antonio, 
      San Antonio, Texas.
FAU - Egilmez, Nejat K
AU  - Egilmez NK
AUID- ORCID: 0000-0002-2544-2767
AD  - Department of Microbiology and Immunology, University of Louisville, Louisville, 
      Kentucky.
FAU - Sauter, Edward R
AU  - Sauter ER
AD  - Division of Cancer Prevention, NIH/NCI, Bethesda, Maryland.
FAU - Li, Bing
AU  - Li B
AD  - Department of Microbiology and Immunology, University of Louisville, Louisville, 
      Kentucky. b.li@louisville.edu.
LA  - eng
GR  - R01 AI137324/AI/NIAID NIH HHS/United States
GR  - R01 CA180986/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210816
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Dietary Fats)
RN  - 0 (Fatty Acid-Binding Proteins)
RN  - 0 (Linoleic Acids)
SB  - IM
MH  - Animals
MH  - Dietary Fats/*toxicity
MH  - Fatty Acid-Binding Proteins/genetics/*metabolism
MH  - Female
MH  - Linoleic Acids/*toxicity
MH  - Mammary Neoplasms, Experimental/immunology/metabolism/*pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitochondria/metabolism/*pathology
MH  - Obesity/physiopathology
MH  - T-Lymphocytes/drug effects/*immunology
MH  - Thinness/physiopathology
PMC - PMC8530923
MID - NIHMS1735414
COIS- Disclosure of Potential Conflicts of Interest The authors state no conflict of 
      interest
EDAT- 2021/08/18 06:00
MHDA- 2022/01/07 06:00
PMCR- 2022/04/15
CRDT- 2021/08/17 06:37
PHST- 2021/03/08 00:00 [received]
PHST- 2021/07/15 00:00 [revised]
PHST- 2021/08/13 00:00 [accepted]
PHST- 2021/08/18 06:00 [pubmed]
PHST- 2022/01/07 06:00 [medline]
PHST- 2021/08/17 06:37 [entrez]
PHST- 2022/04/15 00:00 [pmc-release]
AID - 0008-5472.CAN-21-0757 [pii]
AID - 10.1158/0008-5472.CAN-21-0757 [doi]
PST - ppublish
SO  - Cancer Res. 2021 Oct 15;81(20):5296-5310. doi: 10.1158/0008-5472.CAN-21-0757. 
      Epub 2021 Aug 16.