دورية أكاديمية
ALDH1A1 promotes immune escape of tumor cells through ZBTB7B-glycolysis pathway.
| العنوان: | ALDH1A1 promotes immune escape of tumor cells through ZBTB7B-glycolysis pathway. |
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| المؤلفون: | Wang M; Department of Geratic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.; Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China., Wang T; Department of Pathology, the Affiliated Zhuzhou Hospital Xiangya Medical College, Central South University, Zhuzhou, Hunan, China., Wang J; Department of Gynaecology, the Affiliated Zhuzhou Hospital Xiangya Medical College, Central South University, Zhuzhou, Hunan, China., Yang Y; Department of Oncology, the Affiliated Zhuzhou Hospital Xiangya Medical College, Central South University, Zhuzhou, Hunan, China., Li X; Department of Geratic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China. xilixyyy@163.com.; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China. xilixyyy@163.com.; Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China. xilixyyy@163.com., Chen H; Department of Gynaecology, the Affiliated Zhuzhou Hospital Xiangya Medical College, Central South University, Zhuzhou, Hunan, China. chenhuancsu@163.com., Liao J; Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Changsha, China. liaojingnanalice@outlook.com. |
| المصدر: | Cell death & disease [Cell Death Dis] 2024 Aug 07; Vol. 15 (8), pp. 568. Date of Electronic Publication: 2024 Aug 07. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101524092 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-4889 (Electronic) NLM ISO Abbreviation: Cell Death Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : Nature Pub. Group |
| مواضيع طبية MeSH: | Glycolysis* , Aldehyde Dehydrogenase 1 Family*/metabolism , Aldehyde Dehydrogenase 1 Family*/genetics , Retinal Dehydrogenase*/metabolism , Retinal Dehydrogenase*/genetics , Mice, Nude* , Tumor Escape*, Humans ; Animals ; Mice ; Cell Line, Tumor ; Transcription Factors/metabolism ; Transcription Factors/genetics ; Gene Expression Regulation, Neoplastic ; Neoplasms/immunology ; Neoplasms/genetics ; Neoplasms/pathology ; DNA-Binding Proteins/metabolism ; DNA-Binding Proteins/genetics ; Immune Checkpoint Inhibitors/pharmacology ; Immune Checkpoint Inhibitors/therapeutic use ; Promoter Regions, Genetic/genetics ; L-Lactate Dehydrogenase/metabolism ; L-Lactate Dehydrogenase/genetics ; Female ; Xenograft Model Antitumor Assays |
| مستخلص: | The primary impediment to the success of immunotherapy lies in the immune evasion orchestrated by tumors, contributing to the suboptimal overall response rates observed. Despite this recognition, the intricacies of the underlying mechanisms remain incompletely understood. Through preliminary detection of clinical patient tissues, we have found that ALDH1A1 was a key gene for the prognosis of cancer patients and tumor glycolysis. In vitro experiments and tumor formation in nude mice suggested that targeting ALDH1A1 could inhibit tumor growth. Through further analysis of xenograft tumor models in immune-normal mice and flow cytometry, we found that deficiency in ALDH1A1 could promote immune system suppression of tumors in vivo. Specifically, RNA-seq analysis, combined with qPCR and western blot, identified the transcription factor ZBTB7B as downstream of ALDH1A1. The binding sites of the transcription factor ZBTB7B on the LDHA promoter region, which is responsible for regulating the rate-limiting enzyme gene LDHA in glycolysis, were determined using luciferase reporter gene detection and Chip-qPCR, respectively. In addition, the increased SUMOylation of ZBTB7B stabilized its transcriptional activity. Further in vivo and in vitro experiments confirmed that the combination of targeting ALDH1A1 and ZBTB7B with immune checkpoint inhibitors could synergistically inhibit tumors in vivo. Finally, after conducting additional verification of patient tissue and clinical data, we have confirmed the potential translational value of targeting ALDH1A1 and ZBTB7B for tumor immunotherapy. These results emphasize the potential translational significance of targeting ALDH1A1 and ZBTB7B in the realm of tumor immunotherapy. The convergence of ALDH1A1 inhibition and immune checkpoint blockade, particularly with PD-L1/PD-1 mAb, presents a compelling avenue for curtailing tumor immune escape. (© 2024. The Author(s).) |
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| المشرفين على المادة: | EC 1.2.1 (Aldehyde Dehydrogenase 1 Family) EC 1.2.1.36 (Retinal Dehydrogenase) EC 1.2.1.36 (ALDH1A1 protein, human) 0 (Transcription Factors) EC 1.1.1.27 (LDHA protein, human) 0 (DNA-Binding Proteins) 0 (Immune Checkpoint Inhibitors) EC 1.1.1.27 (L-Lactate Dehydrogenase) |
| تواريخ الأحداث: | Date Created: 20240806 Date Completed: 20240806 Latest Revision: 20240809 |
| رمز التحديث: | 20240809 |
| مُعرف محوري في PubMed: | PMC11303523 |
| DOI: | 10.1038/s41419-024-06943-9 |
| PMID: | 39107297 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 2041-4889 |
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| DOI: | 10.1038/s41419-024-06943-9 |