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基于炎症细胞、PD-1/PD-L1 信号通路和 M2 巨噬细胞的免疫表型可预测胃癌患者的生存情况。

Immunophenotype based on inflammatory cells, PD-1/PD-L1 signalling pathway and M2 macrophages predicts survival in gastric cancer.

机构信息

Department of Surgery, Central Finland Central Hospital, Jyväskylä, Finland.

Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, University of Oulu, and Oulu University Hospital, Oulu, Finland.

出版信息

Br J Cancer. 2020 Nov;123(11):1625-1632. doi: 10.1038/s41416-020-01053-7. Epub 2020 Sep 18.

DOI:10.1038/s41416-020-01053-7
PMID:32943749
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7687887/
Abstract

BACKGROUND

Immune response against cancer has prognostic impact but its role in gastric cancer is poorly known. The aim of the study was to assess the prognostic significance of immune cell score (CD3+, CD8+), tumour immune escape (PD-L1, PD-1) and immune tolerance (Clever-1).

METHODS

After exclusion of Epstein-Barr virus positive (n = 4) and microsatellite instable (n = 6) tumours, the study included 122 patients with GC undergoing D2 gastrectomy. CD3+ and CD8+ based ICS, PD-L1, PD-1 and Clever-1 expressions were evaluated. Differences in survival were examined using Cox regression adjusted for confounders. The primary outcome was 5-year survival.

RESULTS

The 5-year overall survival rate was 43.4%. High ICS was associated with improved overall survival (adjusted HR 0.48 (95% CI 0.26-0.87)) compared to low ICS. In the high ICS group, patients with PD-L1 expression (5-year survival 69.2 vs. 53.1%, p = 0.317), high PD-1 (5-year survival 70.6 vs. 55.3% p = 0.312) and high Clever-1 (5-year survival 72.0% vs. 45.5% (p = 0.070) had poor prognosis.

CONCLUSIONS

High ICS was associated with improved survival. In the high ICS group, patients with high PD-L1, PD-1 and Clever-1 had poor prognosis highlighting the importance of immune escape and immune tolerance in GC.

摘要

背景

针对癌症的免疫反应具有预后影响,但胃癌中的作用知之甚少。本研究旨在评估免疫细胞评分(CD3+、CD8+)、肿瘤免疫逃逸(PD-L1、PD-1)和免疫耐受(Clever-1)的预后意义。

方法

排除 EBV 阳性(n=4)和微卫星不稳定(n=6)肿瘤后,本研究纳入 122 例行 D2 胃切除术的 GC 患者。评估了 CD3+和 CD8+基础免疫细胞评分(ICS)、PD-L1、PD-1 和 Clever-1 的表达。使用 Cox 回归调整混杂因素后,检查了生存差异。主要结局为 5 年生存率。

结果

5 年总生存率为 43.4%。与低 ICS 相比,高 ICS 与改善的总体生存率相关(调整后的 HR 0.48(95%CI 0.26-0.87))。在高 ICS 组中,PD-L1 表达(5 年生存率 69.2% vs. 53.1%,p=0.317)、高 PD-1(5 年生存率 70.6% vs. 55.3%,p=0.312)和高 Clever-1(5 年生存率 72.0% vs. 45.5%,p=0.070)的患者预后较差。

结论

高 ICS 与生存改善相关。在高 ICS 组中,PD-L1、PD-1 和 Clever-1 高表达的患者预后较差,这突出了免疫逃逸和免疫耐受在 GC 中的重要性。

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Int J Clin Exp Pathol. 2015 Sep 1;8(9):11084-91. eCollection 2015.
信号淋巴细胞激活分子家族成员11(SIGLEC11)通过AKT-雷帕霉素靶蛋白(mTOR)信号传导促进M2巨噬细胞极化,并促进胃癌进展。
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Molecular Mechanism for Malignant Progression of Gastric Cancer Within the Tumor Microenvironment.肿瘤微环境中胃癌恶性进展的分子机制。
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Pathways and molecules for overcoming immunotolerance in metastatic gastrointestinal tumors.转移性胃肠道肿瘤中克服免疫耐受的途径和分子
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CD3+ and CD8+ T cell-based immune cell score as a prognostic factor in clear-cell renal cell carcinoma.基于 CD3+ 和 CD8+ T 细胞的免疫细胞评分作为肾透明细胞癌的预后因素。
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