دورية أكاديمية
PGAM1 Inhibition Promotes HCC Ferroptosis and Synergizes with Anti‐PD‐1 Immunotherapy
| العنوان: | PGAM1 Inhibition Promotes HCC Ferroptosis and Synergizes with Anti‐PD‐1 Immunotherapy |
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| المؤلفون: | Yimin Zheng, Yining Wang, Zhou Lu, Jinkai Wan, Lulu Jiang, Danjun Song, Chuanyuan Wei, Chao Gao, Guoming Shi, Jian Zhou, Jia Fan, Aiwu Ke, Lu Zhou, Jiabin Cai |
| المصدر: | Advanced Science, Vol 10, Iss 29, Pp n/a-n/a (2023) |
| بيانات النشر: | Wiley, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Science |
| مصطلحات موضوعية: | carcinogen metabolism, ferroptosis, hepatocellular carcinoma, immunotherapy, Science |
| الوصف: | Abstract The combination of immunotherapy and molecular targeted therapy exhibits promising therapeutic efficacy in hepatocellular carcinoma (HCC), but the underlying mechanism is still unclear. Here, phosphoglycerate mutase 1 (PGAM1) is identified as a novel immunometabolic target by using a bioinformatic algorithm based on multiple HCC datasets. PGAM1 is highly expressed in HCC and associated with a poor prognosis and a poor response to immunotherapy. In vitro and in vivo experiments indicate that targeting PGAM1 inhibited HCC cell growth and promoted the infiltration of CD8+ T‐cells due to decreased enzymatic activity. Mechanistically, inhibition of PGAM1 promotes HCC cell ferroptosis by downregulating Lipocalin (LCN2) by inducing energy stress and ROS‐dependent AKT inhibition, which can also downregulate Programmed death 1‐ligand 1 (PD‐L1). Moreover, an allosteric PGAM1 inhibitor (KH3) exhibits good antitumor effects in patient‐derived xenograft (PDX) models and enhanced the efficacy of anti‐PD‐1 immunotherapy in subcutaneous and orthotopic HCC models. Taken together, the findings demonstrate that PGAM1 inhibition exerts an antitumor effect by promoting ferroptosis and CD8+ T‐cell infiltration and can synergize with anti‐PD‐1 immunotherapy in HCC. Targeting PGAM1 can be a promising new strategy of “killing two birds with one stone” for HCC treatment. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2198-3844 20230192 |
| Relation: | https://doaj.org/toc/2198-3844 |
| DOI: | 10.1002/advs.202301928 |
| URL الوصول: | https://doaj.org/article/15126f03d9824effbdca99cc5e848d12 |
| رقم الأكسشن: | edsdoj.15126f03d9824effbdca99cc5e848d12 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 21983844 20230192 |
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| DOI: | 10.1002/advs.202301928 |