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LILRB1(+) 免疫细胞浸润可识别卵巢癌患者的免疫抑制微环境及不良预后

英文原题:LILRB1(+) immune cell infiltration identifies immunosuppressive microenvironment and dismal outcomes of patients with ovarian cancer.

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LILRB1(+) immune cell infiltration identifies immunosuppressive microenvironment and dismal outcomes of patients with ovarian cancer.

PubMed 2023/04/17(内容时间) Int Immunopharmacol Q1 · IF 5.6(JCR 2025)

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研究概要

肿瘤浸润性 LILRB1+ ICs 可作为独立的临床预后指标和 OC 治疗反应的预测性生物标志物。未来应开展针对 LILRB1 通路的进一步研究。

研究思路结论见上方概要

免疫检查点抑制剂常用于多种类型的癌症,但其在卵巢癌(OC)中的疗效有限。因此,识别新的免疫相关治疗靶点至关重要。白细胞免疫球蛋白样受体亚家族B1(LILRB1)是人类白细胞抗原G(HLA-G)的关键受体,参与免疫耐受,但其在肿瘤免疫中的作用仍不清楚。

本研究采用免疫荧光技术鉴定LILRB1在OC中的定位。回顾性分析217例OC患者中LILRB1表达对临床结局的影响。纳入TCGA数据库中585例OC患者,探讨LILRB1与肿瘤微环境特征之间的关系。

LILRB1被发现表达于肿瘤细胞(TCs)和免疫细胞(ICs)中。LILRB1+ICs高表达,而非LILRB1+TCs,与OC患者晚期FIGO分期、较短的生存结局和较差的辅助化疗反应相关。LILRB1表达还与高M2巨噬细胞浸润、树突状细胞活化降低以及CD8+T细胞功能障碍相关,提示免疫抑制表型。LILRB1+ICs与CD8+T细胞水平的联合可用于区分具有不同临床生存结果的患者。此外,LILRB1+ICs浸润伴CD8+T细胞缺失提示对抗PD-1/PD-L1治疗的反应较差。

展开英文摘要原文

Immune checkpoint inhibitors are commonly used in various types of cancer, but their efficacy in ovarian cancer (OC) is limited. Thus, identifying novel immune-related therapeutic targets is crucial. Leukocyte immunoglobulin-like receptor subfamily B1 (LILRB1), a key receptor of human leukocyte antigen G (HLA-G), is involved in immune tolerance, but its role in tumor immunity remains unclear.

In this study, immunofluorescence was used to identify the location of LILRB1 in OC. The effect of LILRB1 expression on clinical outcomes in 217 patients with OC was analyzed retrospectively. A total of 585 patients with OC from the TCGA database were included to explore the relationship between LILRB1 and tumor microenvironment characteristics.

LILRB1 was found to be expressed in tumor cells (TCs) and immune cells (ICs). High LILRB1 + ICs, but not LILRB1 + TCs, were associated with advanced FIGO stage, shorter survival outcomes, and worse adjuvant chemotherapy responses in OC patients. LILRB1 expression was also associated with high M2 macrophage infiltration, reduced activation of dendritic cells, and dysfunction of CD8 + T cells, suggesting an immunosuppressive phenotype. The combination of LILRB1 + ICs and CD8 + T cell levels could be used to distinguish patients with different clinical survival results. Moreover, LILRB1 + ICs infiltration with CD8 + T cells absence indicated inferior responsiveness to anti-PD-1/PD-L1 therapy.

Tumor-infiltrating LILRB1 + ICs could be applied as an independent clinical prognosticator and a predictive biomarker for therapy responsiveness to OC. Further studies targeting the LILRB1 pathway should be conducted in the future.

论文信息

作者
Xu X、Yin S、Wang Y、Zhu Q、Zheng G、Lu Y、Li T、Zhu C
第一作者单位
Department of Gynecology and Obstetrics, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China; Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China.China
通讯作者单位
Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China; Guangdong Provincial Key Laboratory of Digestive Cancer Research, Shenzhen, Guangdong, China. Electronic address: zhuchm3@mail.sysu.edu.cn.China
期刊
International immunopharmacology2023 Jun
原文标识
PubMed 37075669 · DOI 10.1016/j.intimp.2023.110162