Metabolic control of CD47 expression through LAT2-mediated amino acid uptake promotes tumor immune evasion

• DOI: 10.1038/s41467-022-34064-4
• Publication Date: 2022-10-23T06:02:59Z
• Authors: Zenan Wang; Binghao Li; Shan Li; Wenlong Lin; Zhan Wang; Shengdong Wang; Weida Chen; Wei Shi; Tao Chen; Hao Zhou; Eloy Yinwang; Wenkan Zhang; Haochen Mou; Xupeng Chai; Jiahao Zhang; Zhimin Lu; Zhaoming Ye
• Keywords: Amino acid transporter; CD47; Glutaminolysis

Abstract Chemotherapy elicits tumor immune evasion with poorly characterized mechanisms. Here, we demonstrate that chemotherapy markedly enhances the expression levels of CD47 in osteosarcoma tissues, which are positively associated patient mortality. We reveal macrophages response to secrete interleukin-18, turn upregulates L-amino acid transporter 2 (LAT2) cells for substantially enhanced uptakes leucine and glutamine, two potent stimulators mTORC1. The increased glutaminolysis activate mTORC1 subsequent c-Myc-mediated transcription CD47. Depletion LAT2 or treatment a LAT inhibitor downregulates macrophage infiltration phagocytosis cells, sensitizes doxorubicin mice. These findings unveil mutual regulation between plays critical role underscore potential intervene LAT2-mediated amino uptake improving cancer therapies.