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肿瘤衍生肽聚糖识别蛋白 2 预测肝细胞癌的生存和抗肿瘤免疫反应。

Tumor-Derived Peptidoglycan Recognition Protein 2 Predicts Survival and Antitumor Immune Responses in Hepatocellular Carcinoma.

机构信息

School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.

Department of Gastrointestinal Medical Oncology, Third Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

Hepatology. 2020 May;71(5):1626-1642. doi: 10.1002/hep.30924. Epub 2020 Jan 24.

DOI:10.1002/hep.30924
PMID:31479523
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7318564/
Abstract

BACKGROUND AND AIMS

Hepatocellular carcinoma (HCC) is linked to immunosuppression. Relieving immunosuppression has been an attractive strategy to improve the efficacy of cancer immunotherapy. Peptidoglycan recognition protein 2 (PGLYRP2) is a pattern recognition receptor which is specifically expressed in liver and implicated in the regulation of innate immunity and immunosurveillance. However, the role of hepatic PGLYRP2 in modulating immune responses against HCC remains to be investigated.

APPROACH AND RESULTS

In this study, we investigated whether PGLYRP2 is able to influence HCC progression through regulating host antitumor immune responses. We demonstrated that PGLYRP2 was down-regulated in HCC, which was linked with poor prognosis in patients (P < 0.001). PGLYRP2 overexpression in HCC cells significantly enhanced antitumor immune responses in immune-competent mice and elevated immune response rates of peripheral blood mononuclear cells against HCC. Mechanistically, DNA methyltransferase 3A-mediated promoter hypermethylation was responsible for the down-regulation of PGLYRP2 in HCC. PGLYRP2 promoted production of chemokine (C-C motif) ligand 5 (CCL5) in HCC through binding to the CCL5 promoter, which contributed to the enhanced antitumor immunity.

CONCLUSIONS

We provide evidence that tumor-derived PGLYRP2 acts as a candidate biomarker for adequate immune response against HCC and improved patient outcomes, indicating the importance of hepatic PGLYRP2 in cancer immunosurveillance and in designing immunotherapeutic approaches.

摘要

背景与目的

肝细胞癌（HCC）与免疫抑制有关。减轻免疫抑制一直是提高癌症免疫治疗效果的一种有吸引力的策略。肽聚糖识别蛋白 2（PGLYRP2）是一种模式识别受体，特异性表达于肝脏，参与固有免疫和免疫监视的调节。然而，肝 PGLYRP2 在调节针对 HCC 的免疫反应中的作用仍有待研究。

方法和结果

在这项研究中，我们研究了 PGLYRP2 是否能够通过调节宿主抗肿瘤免疫反应来影响 HCC 的进展。我们发现 PGLYRP2 在 HCC 中下调，与患者的预后不良相关（P<0.001）。在免疫功能正常的小鼠中，HCC 细胞中 PGLYRP2 的过表达显著增强了抗肿瘤免疫反应，并提高了外周血单核细胞对 HCC 的免疫反应率。机制上，DNA 甲基转移酶 3A 介导的启动子超甲基化导致 HCC 中 PGLYRP2 的下调。PGLYRP2 通过与 CCL5 启动子结合促进 HCC 中趋化因子（C-C 基序）配体 5（CCL5）的产生，从而增强抗肿瘤免疫。

结论

我们提供的证据表明，肿瘤来源的 PGLYRP2 可作为针对 HCC 的适当免疫反应和改善患者预后的候选生物标志物，表明肝 PGLYRP2 在癌症免疫监视和设计免疫治疗方法中的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8301/7318564/209f9d037738/HEP-71-1626-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8301/7318564/fb4d9184b26c/HEP-71-1626-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8301/7318564/8ccb3c9590d5/HEP-71-1626-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8301/7318564/c210dd098ebd/HEP-71-1626-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8301/7318564/deb2ab72e506/HEP-71-1626-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8301/7318564/58e8564ae2ca/HEP-71-1626-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8301/7318564/af1108680e9a/HEP-71-1626-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8301/7318564/209f9d037738/HEP-71-1626-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8301/7318564/fb4d9184b26c/HEP-71-1626-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8301/7318564/8ccb3c9590d5/HEP-71-1626-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8301/7318564/c210dd098ebd/HEP-71-1626-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8301/7318564/deb2ab72e506/HEP-71-1626-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8301/7318564/58e8564ae2ca/HEP-71-1626-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8301/7318564/af1108680e9a/HEP-71-1626-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8301/7318564/209f9d037738/HEP-71-1626-g007.jpg

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本文引用的文献

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2
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Clin Cancer Res. 2019 Mar 1;25(5):1612-1623. doi: 10.1158/1078-0432.CCR-18-1932. Epub 2018 Dec 11.
3
Human breast tumor-infiltrating CD8 T cells retain polyfunctionality despite PD-1 expression.
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J Immunother Cancer. 2025 May 22;13(5):e011427. doi: 10.1136/jitc-2024-011427.
4
Identifcation of candidate biomarkers for polyarteritis nodosa using data-independent acquisition mass spectrometry.使用数据非依赖采集质谱法鉴定结节性多动脉炎的候选生物标志物。
Am J Transl Res. 2025 Jan 15;17(1):585-602. doi: 10.62347/QSRI6160. eCollection 2025.
5
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J Clin Invest. 2025 Feb 13;135(8). doi: 10.1172/JCI188083. eCollection 2025 Apr 15.
6
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7
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Nat Rev Gastroenterol Hepatol. 2025 Mar;22(3):191-205. doi: 10.1038/s41575-024-01024-w. Epub 2024 Dec 11.
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