Metabolic engineering of SLC38A2 reprograms glutamine utilization and enhances CAR-macrophage antitumor function in solid tumors.
[OBJECTIVE] This study was aimed at investigating metabolic dysregulation in tumor-associated macrophages (TAMs) in breast cancer and developing a metabolically enhanced chimeric antigen receptor macr
APA
Liu M, Chen Q, et al. (2026). Metabolic engineering of SLC38A2 reprograms glutamine utilization and enhances CAR-macrophage antitumor function in solid tumors.. Cancer biology & medicine, 23(3), 392-417. https://doi.org/10.20892/j.issn.2095-3941.2025.0775
MLA
Liu M, et al.. "Metabolic engineering of SLC38A2 reprograms glutamine utilization and enhances CAR-macrophage antitumor function in solid tumors.." Cancer biology & medicine, vol. 23, no. 3, 2026, pp. 392-417.
PMID
41925028
Abstract
[OBJECTIVE] This study was aimed at investigating metabolic dysregulation in tumor-associated macrophages (TAMs) in breast cancer and developing a metabolically enhanced chimeric antigen receptor macrophage (CAR-M) strategy to boost antitumor potency in solid tumors.
[METHODS] Integrated scRNA-seq and metabolomic analyses were performed to characterize metabolic alterations in macrophages within the breast cancer tumor microenvironment (TME). According to the identified metabolic vulnerabilities, SLC38A2-overexpressing anti-HER2 CAR-Ms were engineered. Glutamine uptake and phagocytic activity were assessed to evaluate functional enhancement.
[RESULTS] TAMs in breast cancer exhibited substantial metabolic dysregulation, particularly impaired glutamine metabolism accompanied by decreased expression of the glutamine transporter SLC38A2. Overexpression of SLC38A2 in anti-HER2 CAR-Ms, compared with conventional anti-HER2 CAR-Ms, enhanced glutamine uptake and markedly augmented phagocytosis of HER2 breast cancer cells.
[CONCLUSIONS] Metabolic engineering SLC38A2 restored glutamine fitness and enhanced the antitumor activity of HER2-targeted CAR-Ms, thus providing a promising strategy to boost CAR-M-mediated tumor suppression in solid tumors.
[METHODS] Integrated scRNA-seq and metabolomic analyses were performed to characterize metabolic alterations in macrophages within the breast cancer tumor microenvironment (TME). According to the identified metabolic vulnerabilities, SLC38A2-overexpressing anti-HER2 CAR-Ms were engineered. Glutamine uptake and phagocytic activity were assessed to evaluate functional enhancement.
[RESULTS] TAMs in breast cancer exhibited substantial metabolic dysregulation, particularly impaired glutamine metabolism accompanied by decreased expression of the glutamine transporter SLC38A2. Overexpression of SLC38A2 in anti-HER2 CAR-Ms, compared with conventional anti-HER2 CAR-Ms, enhanced glutamine uptake and markedly augmented phagocytosis of HER2 breast cancer cells.
[CONCLUSIONS] Metabolic engineering SLC38A2 restored glutamine fitness and enhanced the antitumor activity of HER2-targeted CAR-Ms, thus providing a promising strategy to boost CAR-M-mediated tumor suppression in solid tumors.
MeSH Terms
Glutamine; Humans; Female; Mice; Animals; Tumor Microenvironment; Metabolic Engineering; Breast Neoplasms; Tumor-Associated Macrophages; Cell Line, Tumor; Receptors, Chimeric Antigen; Erb-b2 Receptor Tyrosine Kinases; Macrophages; Phagocytosis; Xenograft Model Antitumor Assays; Immunotherapy, Adoptive
같은 제1저자의 인용 많은 논문 (5)
- CDH17 facilitates β-catenin nuclear translocation to reduce drug sensitivity in cisplatin-resistant gastric cancer cells.
- Cost-effectiveness analysis of tepotinib vs capmatinib as subsequent therapy in MET exon 14-mutated non-small-cell lung cancer.
- Triangulating Associations Between Fruit Intake and Lung Cancer Risk: Evidence from GBD Estimates, Mendelian Randomization, and Real-World Validation.
- Cell-free supernatant of Clostridium butyricum induces mitochondrial apoptosis and suppresses NF-κB pathway in colorectal cancer cells.
- Case Report: Olaparib combined with temozolomide and atezolizumab in a case of -mutated small-cell transformation of lung adenocarcinoma.