PMID- 38412100
OWN - NLM
STAT- MEDLINE
DCOM- 20240401
LR  - 20240401
IS  - 2211-1247 (Electronic)
VI  - 43
IP  - 3
DP  - 2024 Mar 26
TI  - IL-37 dampens immunosuppressive functions of MDSCs via metabolic reprogramming in 
      the tumor microenvironment.
PG  - 113835
LID - S2211-1247(24)00163-3 [pii]
LID - 10.1016/j.celrep.2024.113835 [doi]
AB  - Interleukin-37 (IL-37) has been shown to inhibit tumor growth in various cancer 
      types. However, the immune regulatory function of IL-37 in the tumor 
      microenvironment is unclear. Here, we established a human leukocyte antigen-I 
      (HLA-I)-matched humanized patient-derived xenograft hepatocellular carcinoma 
      (HCC) model and three murine orthotopic HCC models to study the function of IL-37 
      in the tumor microenvironment. We found that IL-37 inhibited HCC growth and 
      promoted T cell activation. Further study revealed that IL-37 impaired the 
      immunosuppressive capacity of myeloid-derived suppressor cells (MDSCs). 
      Pretreatment of MDSCs with IL-37 before adoptive transfer attenuated their 
      tumor-promoting function in HCC tumor-bearing mice. Moreover, IL-37 promoted both 
      glycolysis and oxidative phosphorylation in MDSCs, resulting in the upregulation 
      of ATP release, which impaired the immunosuppressive capacity of MDSCs. 
      Collectively, we demonstrated that IL-37 inhibited tumor development through 
      dampening MDSCs' immunosuppressive capacity in the tumor microenvironment via 
      metabolic reprogramming, making it a promising target for future cancer 
      immunotherapy.
CI  - Copyright (c) 2024 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Mei, Yu
AU  - Mei Y
AD  - Immunology Program, Life Sciences Institute, Immunology Translational Research 
      Program, and Department of Microbiology and Immunology, Yong Loo Lin School of 
      Medicine, National University of Singapore, Singapore 117456, Singapore.
FAU - Zhu, Ying
AU  - Zhu Y
AD  - Immunology Program, Life Sciences Institute, Immunology Translational Research 
      Program, and Department of Microbiology and Immunology, Yong Loo Lin School of 
      Medicine, National University of Singapore, Singapore 117456, Singapore.
FAU - Yong, Kylie Su Mei
AU  - Yong KSM
AD  - Institute of Molecular and Cell Biology, Agency for Science, Technology, and 
      Research (ASTAR), Singapore 138673, Singapore.
FAU - Hanafi, Zuhairah Binte
AU  - Hanafi ZB
AD  - Immunology Program, Life Sciences Institute, Immunology Translational Research 
      Program, and Department of Microbiology and Immunology, Yong Loo Lin School of 
      Medicine, National University of Singapore, Singapore 117456, Singapore.
FAU - Gong, Huanle
AU  - Gong H
AD  - Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of 
      Hematology, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow 
      University, Soochow University, Suzhou 215006, P.R. China.
FAU - Liu, Yonghao
AU  - Liu Y
AD  - Immunology Program, Life Sciences Institute, Immunology Translational Research 
      Program, and Department of Microbiology and Immunology, Yong Loo Lin School of 
      Medicine, National University of Singapore, Singapore 117456, Singapore.
FAU - Teo, Huey Yee
AU  - Teo HY
AD  - Immunology Program, Life Sciences Institute, Immunology Translational Research 
      Program, and Department of Microbiology and Immunology, Yong Loo Lin School of 
      Medicine, National University of Singapore, Singapore 117456, Singapore.
FAU - Hussain, Muslima
AU  - Hussain M
AD  - Immunology Program, Life Sciences Institute, Immunology Translational Research 
      Program, and Department of Microbiology and Immunology, Yong Loo Lin School of 
      Medicine, National University of Singapore, Singapore 117456, Singapore.
FAU - Song, Yuan
AU  - Song Y
AD  - Immunology Program, Life Sciences Institute, Immunology Translational Research 
      Program, and Department of Microbiology and Immunology, Yong Loo Lin School of 
      Medicine, National University of Singapore, Singapore 117456, Singapore.
FAU - Chen, Qingfeng
AU  - Chen Q
AD  - Institute of Molecular and Cell Biology, Agency for Science, Technology, and 
      Research (ASTAR), Singapore 138673, Singapore. Electronic address: 
      qchen@imcb.a-star.edu.sg.
FAU - Liu, Haiyan
AU  - Liu H
AD  - Immunology Program, Life Sciences Institute, Immunology Translational Research 
      Program, and Department of Microbiology and Immunology, Yong Loo Lin School of 
      Medicine, National University of Singapore, Singapore 117456, Singapore. 
      Electronic address: micliuh@nus.edu.sg.
LA  - eng
PT  - Journal Article
DEP - 20240226
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - *Myeloid-Derived Suppressor Cells
MH  - *Carcinoma, Hepatocellular/metabolism
MH  - *Liver Neoplasms/metabolism
MH  - Metabolic Reprogramming
MH  - Tumor Microenvironment
OTO - NOTNLM
OT  - ATP
OT  - CP: Cancer
OT  - CP: Immunology
OT  - Interleukin-37
OT  - hepatocellular carcinoma
OT  - metabolism
OT  - myeloid-derived suppressor cells
COIS- Declaration of interests The authors declare no competing interests.
EDAT- 2024/02/27 18:42
MHDA- 2024/04/01 06:43
CRDT- 2024/02/27 12:36
PHST- 2023/05/30 00:00 [received]
PHST- 2023/12/18 00:00 [revised]
PHST- 2024/02/06 00:00 [accepted]
PHST- 2024/04/01 06:43 [medline]
PHST- 2024/02/27 18:42 [pubmed]
PHST- 2024/02/27 12:36 [entrez]
AID - S2211-1247(24)00163-3 [pii]
AID - 10.1016/j.celrep.2024.113835 [doi]
PST - ppublish
SO  - Cell Rep. 2024 Mar 26;43(3):113835. doi: 10.1016/j.celrep.2024.113835. Epub 2024 
      Feb 26.