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The E3 Ubiquitin Ligase FBXO38 Maintains the Antitumor Function of Natural Killer Cells by Sustaining IL15R Signaling

Cancer Immunol Res. 2024-10; 
Yongjing Shi , Xiaodong Zheng , Hui Peng , Chenqi Xu , Rui Sun , Zhigang Tian , Haoyu Sun , Xianwei Wang
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Proteins, Expression, Isolation and Analysis Equal amounts of protein lysate were loaded onto 4% to 12% Bis-Tris protein gels (Genscript Biotech, Nanjing, China) and transferred to polyvinylidene difluoride membranes (Millipore, Bedford, MA, USA). Get A Quote

Abstract

Natural killer (NK) cells are the main innate antitumor effector cells but their function is often constrained in the tumor microenvironment. It has been reported that the E3 ligase FBXO38 accelerates PD-1 degradation in tumor-infiltrating T cells to unleash their cytotoxic function. In this study, we found that the transcriptional levels of FBXO38 in intratumoral NK cells of patients with cancer and tumor-bearing mice were significantly lower than in peritumoral NK cells. Conditional knockout of FBXO38 in NK cells accelerated tumor growth and increased tumor metastasis. FBXO38 deficiency resulted in impaired proliferation and survival of tumor-infiltrating NK (TINK) cells. Mechanistically, FBXO38 deficiency en... More

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