Article Text

Download PDFPDF

1057 IL-37 dampens immune suppressive functions of MDSCs via metabolic reprogramming in the tumor microenvironment
  1. Yu Mei1,
  2. Ying Zhu1,
  3. Kylie Su Mei Yong2,
  4. Qingfeng Chen2 and
  5. Haiyan Liu1
  1. 1National University of Singapore, Singapore, NA, Singapore
  2. 22Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Singapore, NA, Singapore
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background 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. Recent studies have suggested that IL-37 could recruit natural killer cells and promote dendritic cell or macrophage functions to inhibit tumor development using subcutaneous or xenograft mouse models, which may not reflect the organ-specific tumor microenvironment.

Methods We established a humanized patient-derived xenograft (PDX) hepatocellular carcinoma (HCC) model and three murine orthotopic HCC models to study the function of IL-37 in the tumor microenvironment.

Results We found that IL-37 inhibited HCC growth and promoted T cell activation. Further study revealed that IL-37 impaired the immune-suppressive 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 OXPHOS in MDSCs, resulting in the upregulation of ATP release, which impaired the immune-suppressive capacity of MDSCs.

Conclusions Taken together, we demonstrated that IL-37 inhibited tumor development through dampening MDSC’s immune-suppressive capacity in the tumor microenvironment via metabolic reprogramming, making it a promising target for future cancer immunotherapy.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.