PMID- 34478917
OWN - NLM
STAT- MEDLINE
DCOM- 20211221
LR  - 20211221
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 576
DP  - 2021 Oct 22
TI  - PPARG-mediated ferroptosis in dendritic cells limits antitumor immunity.
PG  - 33-39
LID - S0006-291X(21)01264-X [pii]
LID - 10.1016/j.bbrc.2021.08.082 [doi]
AB  - Dendritic cells (DCs) are antigen-presenting cells of the immune system, which 
      play a key role in antitumor immunity by activating cytotoxic T cells. Here, we 
      report that elevated ferroptosis, a lipid peroxidation-mediated cell death, 
      impairs the maturation of DCs and their function in tumor suppression. 
      Ferroptosis is selectively induced in DCs by the GXP4 inhibitor RSL3, but not the 
      SLC7A11 inhibitor erastin. Ferroptotic DCs lose their ability to secrete 
      pro-inflammatory cytokines (TNF and IL6) and express MHC class I in response to 
      the maturation signal of lipopolysaccharide. Moreover, ferroptotic DCs fail to 
      induce CD8(+) T cells to produce IFNG/IFNgamma. Mechanistically, PPARG/PPARgamma, a 
      nuclear receptor involved in the regulation of lipid metabolism, is responsible 
      for RSL3-induced ferroptosis in DCs. Consequently, the genetic depletion of PPARG 
      restores the maturation and function of DCs. Using immunogenic cell death-based 
      DC vaccine models, we further demonstrate that PPARG-mediated ferroptosis of DCs 
      limits antitumor immunity in mice. Together, these findings demonstrate a novel 
      role of ferroptotic DCs in driving an immunosuppressive tumor microenvironment.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Han, Leng
AU  - Han L
AD  - Department of Oncology and Hematology, China-Japan Union Hospital of Jilin 
      University, Changchun, Jilin, 130031, China.
FAU - Bai, Lulu
AU  - Bai L
AD  - Department of Pediatric Hematology, First Hospital of Jilin University, 
      Changchun, Jilin, 130021, China.
FAU - Qu, Chunjing
AU  - Qu C
AD  - Department of Oncology and Hematology, China-Japan Union Hospital of Jilin 
      University, Changchun, Jilin, 130031, China.
FAU - Dai, Enyong
AU  - Dai E
AD  - Department of Oncology and Hematology, China-Japan Union Hospital of Jilin 
      University, Changchun, Jilin, 130031, China.
FAU - Liu, Jiao
AU  - Liu J
AD  - The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 
      Guangdong, 510120, China.
FAU - Kang, Rui
AU  - Kang R
AD  - Department of Surgery, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
FAU - Zhou, Di
AU  - Zhou D
AD  - Department of Oncology and Hematology, China-Japan Union Hospital of Jilin 
      University, Changchun, Jilin, 130031, China. Electronic address: 
      zhoudi2013@jlu.edu.cn.
FAU - Tang, Daolin
AU  - Tang D
AD  - Department of Surgery, UT Southwestern Medical Center, Dallas, TX, 75390, USA. 
      Electronic address: daolin.tang@utsouthwestern.edu.
FAU - Zhao, Yanan
AU  - Zhao Y
AD  - Department of Oncology and Hematology, China-Japan Union Hospital of Jilin 
      University, Changchun, Jilin, 130031, China. Electronic address: 
      zhaoyanan1986@jlu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20210829
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (PPAR gamma)
RN  - 0 (Pparg protein, mouse)
SB  - IM
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cell Line, Tumor
MH  - Dendritic Cells/*immunology
MH  - Disease Models, Animal
MH  - Female
MH  - Ferroptosis/immunology
MH  - Immunotherapy/*methods
MH  - Lipid Peroxidation/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - PPAR gamma/genetics/*immunology/metabolism
MH  - Pancreatic Neoplasms/*drug therapy/*immunology/metabolism
OTO - NOTNLM
OT  - Cytokine
OT  - Dendritic cells
OT  - Ferroptosis
OT  - Immunosuppression
OT  - Lipid peroxidation
COIS- Declaration of competing interest The authors declare no conflicts of interest or 
      financial interests.
EDAT- 2021/09/04 06:00
MHDA- 2021/12/22 06:00
CRDT- 2021/09/03 20:15
PHST- 2021/08/06 00:00 [received]
PHST- 2021/08/25 00:00 [revised]
PHST- 2021/08/28 00:00 [accepted]
PHST- 2021/09/04 06:00 [pubmed]
PHST- 2021/12/22 06:00 [medline]
PHST- 2021/09/03 20:15 [entrez]
AID - S0006-291X(21)01264-X [pii]
AID - 10.1016/j.bbrc.2021.08.082 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2021 Oct 22;576:33-39. doi: 
      10.1016/j.bbrc.2021.08.082. Epub 2021 Aug 29.