ArticleNature communications2022
Metabolic control of CD47 expression through LAT2-mediated amino acid uptake promotes tumor immune evasion.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.
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Who cites it
85 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
- From mechanism to therapy: advances in macrophage polarisation and targeted intervention in osteosarcoma.Frontiers in immunology · 2026Pooled it
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- Targeted PD-L1 degradation with an injectable hydrogel reverses chemotherapy-induced compensatory immunosuppression and enhances antitumor immunity.Materials today. Bio · 2026Article
- Hippocampal neural stem cell-derived extracellular vesicles modulate microglia to promote resilience against tau oligomers.Neural regeneration research · 2026Article
- Chemotherapy-Activated GSK3β-DNMT1 Signaling Upregulates CD47 to Evade Macrophage Phagocytosis and Drive Temozolomide Resistance in Glioblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Pulmonary mRNA-LNP vaccines for rapid and durable protection against bacterial infection.Nature communications · 2026Article
- Targeting the PARP10-BCAT2 axis disrupts branched-chain amino-acid metabolism to suppress bone metastasis in lung cancer.Cell death & disease · 2026Article
- Copper Depletion Nanoparticles Potentiate Cancer Immunotherapy by Avoiding Innate and Adaptive Immune Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dynamic remodeling of amino acid metabolism in tumor-associated macrophages: Fueling immunosuppression, reshaping tumor niches, and unlocking metabolic checkpoints.Journal of advanced research · 2026Review
- Amino Acids as Targets for Immunotherapy against Solid Tumors.Cell biochemistry and biophysics · 2026Review
- Engineering Osteoimmune Responses with Functionalized Orthopedic Implants for Post-Operative Osteosarcoma Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- A Targetable Developmental Program Coregulates Angiogenesis and Immune Evasion in Melanoma.Cancer discovery · 2026Article
- ETV4 Promotes Colorectal Cancer Progression by Reprogramming Asparagine Metabolism to Remodel the Stromal Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Overview of glutamine metabolism in stromal components of the tumor microenvironment and potential anti-tumor therapies.Genes & diseases · 2026Review
- Prognostic and Predictive Value of CD163+ Macrophages for Neoadjuvant Chemotherapy in Osteosarcoma.Biomedicines · 2026Article
- Targeting glutamine metabolism to modulate macrophage functions in the tumor microenvironment.Discover oncology · 2026Review
- NAT10 promotes cisplatin resistance and immune escape by increasing the expression of DUSP1 and PD-L1 in gastric cancer.Cell death discovery · 2026Article
- Low-dose DOX-polygodial nanosystem modulates the CD47/CALR axis for safer triple negative breast cancer treatment.Nanoscale advances · 2026Article
- Targeting the PSMD14-BCKDK pathway overcomes immune suppression and enhances CAR-NK infiltration in glioblastoma.Cell death and differentiation · 2026Article
- Solute Carrier transporters in tumor metabolism and immune modulation: implications for therapy.Journal of translational medicine · 2026Review
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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 with patient mortality. We reveal that macrophages in response to chemotherapy secrete interleukin-18, which in turn upregulates expression of L-amino acid transporter 2 (LAT2) in tumor cells for substantially enhanced uptakes of leucine and glutamine, two potent stimulators of mTORC1. The increased levels of leucine and enhanced glutaminolysis activate mTORC1 and subsequent c-Myc-mediated transcription of CD47. Depletion of LAT2 or treatment of tumor cells with a LAT inhibitor downregulates CD47 with enhanced macrophage infiltration and phagocytosis of tumor cells, and sensitizes osteosarcoma to doxorubicin treatment in mice. These findings unveil a mutual regulation between macrophage and tumor cells that plays a critical role in tumor immune evasion and underscore the potential to intervene with the LAT2-mediated amino acid uptake for improving cancer therapies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.