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载脂蛋白 E 通过 NF-κB 介导的 CXCL1 产生促进胰腺癌中的免疫抑制。

Apolipoprotein E Promotes Immune Suppression in Pancreatic Cancer through NF-κB-Mediated Production of CXCL1.

机构信息

Program in Molecular and Cellular Pathology, University of Michigan, Ann Arbor, Michigan.

Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan.

出版信息

Cancer Res. 2021 Aug 15;81(16):4305-4318. doi: 10.1158/0008-5472.CAN-20-3929. Epub 2021 May 28.

DOI:10.1158/0008-5472.CAN-20-3929
PMID:34049975
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8445065/
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with few effective therapeutic options. PDAC is characterized by an extensive fibroinflammatory stroma that includes abundant infiltrating immune cells. Tumor-associated macrophages (TAM) are prevalent within the stroma and are key drivers of immunosuppression. TAMs in human and murine PDAC are characterized by elevated expression of apolipoprotein E (ApoE), an apolipoprotein that mediates cholesterol metabolism and has known roles in cardiovascular and Alzheimer's disease but no known role in PDAC. We report here that ApoE is also elevated in peripheral blood monocytes in PDAC patients, and plasma ApoE protein levels stratify patient survival. Orthotopic implantation of mouse PDAC cells into syngeneic wild-type or in mice showed reduced tumor growth in mice. Histologic and mass cytometric (CyTOF) analysis of these tumors showed an increase in CD8 T cells in tumors in mice. Mechanistically, ApoE induced pancreatic tumor cell expression of and , known immunosuppressive factors, through LDL receptor and NF-κB signaling. Taken together, this study reveals a novel immunosuppressive role of ApoE in the PDAC microenvironment. SIGNIFICANCE: This study shows that elevated apolipoprotein E in PDAC mediates immune suppression and high serum apolipoprotein E levels correlate with poor patient survival..

摘要

胰腺导管腺癌（PDAC）是一种致命的恶性肿瘤，治疗选择有限。PDAC 的特征是广泛的纤维炎症基质，其中包括丰富的浸润免疫细胞。肿瘤相关巨噬细胞（TAM）在基质中普遍存在，是免疫抑制的关键驱动因素。人类和小鼠 PDAC 中的 TAMs 特征是载脂蛋白 E（ApoE）的表达升高，ApoE 是一种载脂蛋白，介导胆固醇代谢，在心血管疾病和阿尔茨海默病中具有已知作用，但在 PDAC 中没有已知作用。我们在这里报告，PDAC 患者的外周血单核细胞中 ApoE 也升高，血浆 ApoE 蛋白水平分层患者的生存情况。将小鼠 PDAC 细胞原位植入同种异体野生型或 小鼠中，显示 小鼠中的肿瘤生长减少。这些肿瘤的组织学和质谱流式细胞术（CyTOF）分析显示， 小鼠肿瘤中的 CD8 T 细胞增加。从机制上讲，ApoE 通过 LDL 受体和 NF-κB 信号通路诱导胰腺肿瘤细胞表达 和 ，这是已知的免疫抑制因子。总之，这项研究揭示了 ApoE 在 PDAC 微环境中的新的免疫抑制作用。意义：本研究表明，PDAC 中升高的载脂蛋白 E 介导免疫抑制，高血清载脂蛋白 E 水平与患者预后不良相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c16/9662877/c271f99ecc02/4305fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c16/9662877/5c39f3382434/4305fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c16/9662877/73237f201162/4305fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c16/9662877/af85d32c9da8/4305fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c16/9662877/ad2d35241ff4/4305fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c16/9662877/0a5f2e442977/4305fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c16/9662877/367e41ba01d5/4305fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c16/9662877/c271f99ecc02/4305fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c16/9662877/5c39f3382434/4305fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c16/9662877/73237f201162/4305fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c16/9662877/af85d32c9da8/4305fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c16/9662877/ad2d35241ff4/4305fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c16/9662877/0a5f2e442977/4305fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c16/9662877/367e41ba01d5/4305fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c16/9662877/c271f99ecc02/4305fig7.jpg

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2
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Cancer Cell. 2020 Oct 12;38(4):567-583.e11. doi: 10.1016/j.ccell.2020.08.015. Epub 2020 Sep 24.
3
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NPJ Precis Oncol. 2025 Aug 20;9(1):292. doi: 10.1038/s41698-025-01091-5.
4
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5
Cancer Vaccination and Immune-Based Approaches in Pancreatic Cancer.胰腺癌的癌症疫苗接种及基于免疫的治疗方法
Cancers (Basel). 2025 Jul 15;17(14):2356. doi: 10.3390/cancers17142356.
6
Primary and metastatic cellular landscapes in human pancreatic cancer.人类胰腺癌的原发性和转移性细胞图谱。
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7
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8
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9
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8
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