IL-37 dampens immunosuppressive functions of MDSCs via metabolic reprogramming in the tumor microenvironment

作者：Yu Mei, Ying Zhu, Kylie Su Mei Yong, Zuhairah Binte Hanafi, Huanle Gong, Yonghao Liu, Huey Yee Teo, Muslima Hussain, Yuan Song, Qingfeng Chen, Haiyan Liu · 发表于：Cell Reports · 年份：2024 · DOI：10.1016/j.celrep.2024.113835 · 被引用次数：27 · 研究领域：Cancer, Hypoxia, and Metabolism、Cancer, Stress, Anesthesia, and Immune Response、Immune cells in cancer

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.