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.
Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China; Guangdong Provincial Key Laboratory of Digestive Cancer Research, Shenzhen, Guangdong, China.
Int Immunopharmacol. 2023 Jun;119:110162. doi: 10.1016/j.intimp.2023.110162. Epub 2023 Apr 17.
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.
免疫检查点抑制剂常用于多种癌症，但在卵巢癌（OC）中的疗效有限。因此，鉴定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，但它在肿瘤免疫中的作用尚不清楚。
本研究采用免疫荧光法鉴定 LILRB1 在 OC 中的位置。回顾性分析 217 例 OC 患者 LILRB1 表达对临床结局的影响。共纳入 TCGA 数据库中 585 例 OC 患者，探讨 LILRB1 与肿瘤微环境特征的关系。
发现 LILRB1 在肿瘤细胞（TCs）和免疫细胞（ICs）中表达。高 LILRB1 ICs，但不是 LILRB1 TCs，与 OC 患者FIGO 分期较晚、生存结局较差和辅助化疗反应较差相关。LILRB1 表达还与 M2 巨噬细胞浸润增加、树突状细胞激活减少和 CD8 T 细胞功能障碍相关，提示存在免疫抑制表型。LILRB1 ICs 与 CD8 T 细胞水平的组合可用于区分具有不同临床生存结果的患者。此外，LILRB1 ICs 浸润而缺乏 CD8 T 细胞表明对抗 PD-1/PD-L1 治疗的反应性较差。
肿瘤浸润的 LILRB1 ICs 可作为独立的临床预后指标和 OC 治疗反应的预测生物标志物。未来应进一步研究针对 LILRB1 途径的治疗方法。
