肿瘤分泌的FGF21通过重塑CD8 T细胞的胆固醇代谢发挥免疫抑制作用。 - Suppr

Tumor-secreted FGF21 acts as an immune suppressor by rewiring cholesterol metabolism of CD8T cells.

作者信息

Hu Cegui, Qiao Wen, Li Xiang, Ning Zhi-Kun, Liu Jiang, Dalangood Sumiya, Li Hanjun, Yu Xiang, Zong Zhen, Wen Zhenke, Gui Jun

出版信息

Cell Metab. 2024 May 7;36(5):1168. doi: 10.1016/j.cmet.2024.03.013. Epub 2024 Mar 26.

DOI:10.1016/j.cmet.2024.03.013

PMID:38537635

Abstract

摘要

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Tumor-secreted FGF21 acts as an immune suppressor by rewiring cholesterol metabolism of CD8T cells.肿瘤分泌的FGF21通过重塑CD8 T细胞的胆固醇代谢发挥免疫抑制作用。

Cell Metab. 2024 May 7;36(5):1168. doi: 10.1016/j.cmet.2024.03.013. Epub 2024 Mar 26.

Tumor-secreted FGF21 acts as an immune suppressor by rewiring cholesterol metabolism of CD8T cells.肿瘤分泌的 FGF21 通过重编 CD8T 细胞的胆固醇代谢来发挥免疫抑制作用。

Cell Metab. 2024 Mar 5;36(3):630-647.e8. doi: 10.1016/j.cmet.2024.01.005. Epub 2024 Feb 2.

FGF21 as a Hepatokine, Adipokine, and Myokine in Metabolism and Diseases.成纤维细胞生长因子21作为一种肝脏因子、脂肪因子和肌肉因子在代谢及疾病中的作用

Front Endocrinol (Lausanne). 2014 Jul 7;5:107. doi: 10.3389/fendo.2014.00107. eCollection 2014.

FGF21 induces autophagy-mediated cholesterol efflux to inhibit atherogenesis via RACK1 up-regulation.成纤维细胞生长因子21通过上调活化C激酶1诱导自噬介导的胆固醇流出以抑制动脉粥样硬化的发生。

J Cell Mol Med. 2020 May;24(9):4992-5006. doi: 10.1111/jcmm.15118. Epub 2020 Mar 30.

Pharmacological treatment with FGF21 strongly improves plasma cholesterol metabolism to reduce atherosclerosis.用 FGF21 进行药物治疗可显著改善血浆胆固醇代谢，从而减少动脉粥样硬化。

Cardiovasc Res. 2022 Jan 29;118(2):489-502. doi: 10.1093/cvr/cvab076.

Rewiring innate and adaptive immunity with TLR9 agonist to treat osteosarcoma.用 TLR9 激动剂重塑固有免疫和适应性免疫以治疗骨肉瘤。

J Exp Clin Cancer Res. 2023 Jun 26;42(1):154. doi: 10.1186/s13046-023-02731-z.

CD8+ T suppressor cells are back to the game: are they players in autoimmunity?CD8 + T抑制细胞再度入局：它们是自身免疫中的参与者吗？

Autoimmun Rev. 2002 Oct;1(5):279-83. doi: 10.1016/s1568-9972(02)00065-4.

The moderate essential amino acid restriction entailed by low-protein vegan diets may promote vascular health by stimulating FGF21 secretion.低蛋白纯素饮食所带来的适度必需氨基酸限制可能通过刺激成纤维细胞生长因子21（FGF21）的分泌来促进血管健康。

Horm Mol Biol Clin Investig. 2016 Feb 12;30(1):/j/hmbci.2017.30.issue-1/hmbci-2015-0056/hmbci-2015-0056.xml. doi: 10.1515/hmbci-2015-0056.

Fibroblast growth factor 21 prevents atherosclerosis by suppression of hepatic sterol regulatory element-binding protein-2 and induction of adiponectin in mice.成纤维细胞生长因子21通过抑制小鼠肝脏中固醇调节元件结合蛋白-2及诱导脂联素生成来预防动脉粥样硬化。

Circulation. 2015 May 26;131(21):1861-71. doi: 10.1161/CIRCULATIONAHA.115.015308. Epub 2015 Mar 20.

inhibition reduces hepatic steatosis via FGF21 and FGFR1 induction.抑制作用通过诱导成纤维细胞生长因子21（FGF21）和成纤维细胞生长因子受体1（FGFR1）减轻肝脏脂肪变性。

JHEP Rep. 2020 Feb 18;2(2):100093. doi: 10.1016/j.jhepr.2020.100093. eCollection 2020 Apr.

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Prominent fibroblast growth factor 21 with less abundant tumor-associated macrophages in hepatic mass of the conditional mgmt-deleted mice using LysM-Cre system.在使用LysM-Cre系统的条件性mgmt缺失小鼠的肝脏肿块中，成纤维细胞生长因子21显著，而肿瘤相关巨噬细胞较少。

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Bi-directional metabolic reprogramming between cancer cells and T cells reshapes the anti-tumor immune response.癌细胞与T细胞之间的双向代谢重编程重塑了抗肿瘤免疫反应。

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IL-4-STAT6-induced high Siglec-G/10 expression aggravates the severe immune suppressive tumor microenvironment and impedes the efficacy of immunotherapy in head and neck squamous cell carcinoma.白细胞介素-4-信号转导子和转录激活子6诱导的高唾液酸结合性免疫球蛋白样凝集素-G/10表达加重了严重的免疫抑制性肿瘤微环境，并阻碍了头颈部鳞状细胞癌免疫治疗的疗效。

J Immunother Cancer. 2025 Jun 10;13(6):e011474. doi: 10.1136/jitc-2025-011474.

Exosomal POU5 F1 derived from TNBC promotes cancer progression by regulating M2 macrophage polarization via inhibiting TRAF6 ubiquitination and activating AKT in macrophage.源自三阴性乳腺癌的外泌体POU5 F1通过抑制巨噬细胞中TRAF6的泛素化和激活AKT来调节M2巨噬细胞极化，从而促进癌症进展。

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Cholesterol biosynthesis induced by radiotherapy inhibits cGAS-STING activation and contributes to colorectal cancer treatment resistance.放疗诱导的胆固醇生物合成抑制cGAS-STING激活并导致结直肠癌治疗抵抗。

Exp Mol Med. 2025 May 12. doi: 10.1038/s12276-025-01457-6.

A functional single-cell metabolic survey identifies Elovl1 as a target to enhance CD8 T cell fitness in solid tumours.一项功能性单细胞代谢研究确定Elovl1是增强实体瘤中CD8 T细胞适应性的一个靶点。

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Adipokines: masterminds of metabolic inflammation.脂肪因子：代谢性炎症的幕后主使

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Proteogenomic Landscape of Breast Ductal Carcinoma Reveals Tumor Progression Characteristics and Therapeutic Targets.乳腺导管癌的蛋白质基因组图谱揭示肿瘤进展特征和治疗靶点。

Adv Sci (Weinh). 2024 Dec;11(46):e2401041. doi: 10.1002/advs.202401041. Epub 2024 Oct 17.

Inhibition of DUSP18 impairs cholesterol biosynthesis and promotes anti-tumor immunity in colorectal cancer.抑制 DUSP18 可抑制结直肠癌的胆固醇生物合成并促进抗肿瘤免疫。

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Tumor-secreted FGF21 acts as an immune suppressor by rewiring cholesterol metabolism of CD8T cells.

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