PMID- 30619288
OWN - NLM
STAT- MEDLINE
DCOM- 20191021
LR  - 20200309
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 9
DP  - 2018
TI  - Ovarian Cancer-Intrinsic Fatty Acid Synthase Prevents Anti-tumor Immunity by 
      Disrupting Tumor-Infiltrating Dendritic Cells.
PG  - 2927
LID - 10.3389/fimmu.2018.02927 [doi]
LID - 2927
AB  - Fatty acid synthase (FASN), the key metabolic enzyme of de novo lipogenesis, 
      provides proliferative and metastatic capacity directly to cancer cells have been 
      described. However, the impact of aberrant activation of this lipogenic enzyme on 
      host anti-tumor immune milieu remains unknown. In this study, we depicted that 
      elevated FASN expression presented in ovarian cancer with more advanced clinical 
      phenotype and correlated with the immunosuppressive status, which characterized 
      by the lower number and dysfunction of infiltrating T cells. Notably, in a mouse 
      model, we showed that tumor cell-intrinsic FASN drove ovarian cancer (OvCa) 
      progression by blunting anti-tumor immunity. Dendritic cells (DCs) are required 
      to initiate and sustain T cell-dependent anti-tumor immunity. Here, our data 
      showed that constitutive activation of FASN in ovarian cancer cell lead to 
      abnormal lipid accumulation and subsequent inhibition of tumor-infiltrating DCs 
      (TIDCs) capacity to support anti-tumor T cells. Mechanistically, FASN activation 
      in ovarian cancer cell-induced the resulting increase of lipids present at high 
      concentrations in the tumor microenvironment. Dendritic cells educated by 
      FASN(high) OvCa ascites are defective in their ability to present antigens and 
      prime T cells. Accordingly, inhibiting FASN by FASN inhibitor can partly restore 
      the immunostimulatory activity of TIDCs and extended tumor control by evoking 
      protective anti-tumor immune responses. Therefore, our data provide a mechanism 
      by which ovarian cancer-intrinsic FASN oncogenic pathway induce the impaired 
      anti-tumor immune response through lipid accumulation in TIDCs and subsequently 
      T-cells exclusion and dysfunction. These results could further indicate that 
      targeting the FASN oncogenic pathway concomitantly enhance anti-tumor immunity, 
      thus offering a unique approach to ovarian cancer immunotherapy.
FAU - Jiang, Li
AU  - Jiang L
AD  - Department of Gynecology and Obstetrics, Xinhua Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
FAU - Fang, Xuhong
AU  - Fang X
AD  - Department of Gynecology and Obstetrics, Xinhua Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
FAU - Wang, Hong
AU  - Wang H
AD  - Department of Gynecology and Obstetrics, Xinhua Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
FAU - Li, Diyou
AU  - Li D
AD  - Department of Gynecology and Obstetrics, Xinhua Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
FAU - Wang, Xipeng
AU  - Wang X
AD  - Department of Gynecology and Obstetrics, Xinhua Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181214
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Lipids)
RN  - EC 2.3.1.85 (Fatty Acid Synthases)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Dendritic Cells/*immunology/metabolism
MH  - Fatty Acid Synthases/genetics/*immunology/metabolism
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/immunology
MH  - Humans
MH  - Lipids/analysis/immunology
MH  - Mice, Inbred C57BL
MH  - Mice, Nude
MH  - Neoplasms, Experimental/genetics/immunology/metabolism
MH  - Ovarian Neoplasms/genetics/*immunology/metabolism
MH  - Signal Transduction/genetics/*immunology
MH  - T-Lymphocytes/immunology/metabolism
MH  - Tumor Microenvironment/genetics/immunology
PMC - PMC6302125
OTO - NOTNLM
OT  - FASN
OT  - immune response
OT  - immunity
OT  - ovarian cancer
OT  - tumor-infiltrating dendritic cells
EDAT- 2019/01/09 06:00
MHDA- 2019/10/23 06:00
PMCR- 2018/01/01
CRDT- 2019/01/09 06:00
PHST- 2018/08/31 00:00 [received]
PHST- 2018/11/29 00:00 [accepted]
PHST- 2019/01/09 06:00 [entrez]
PHST- 2019/01/09 06:00 [pubmed]
PHST- 2019/10/23 06:00 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2018.02927 [doi]
PST - epublish
SO  - Front Immunol. 2018 Dec 14;9:2927. doi: 10.3389/fimmu.2018.02927. eCollection 
      2018.