肺鳞状细胞癌患者肿瘤相关巨噬细胞 SIRPα 表达的临床意义。
Clinical Significance of SIRPα Expression on Tumor-Associated Macrophages in Patients with Lung Squamous Cell Carcinoma.
发表日期:2024 Jun 29
作者:
Taichi Nagano, Kazuki Takada, Fumiya Narutomi, Fumihiko Kinoshita, Takaki Akamine, Mikihiro Kohno, Mototsugu Shimokawa, Tomoyoshi Takenaka, Yoshinao Oda, Tomoharu Yoshizumi
来源:
ANNALS OF SURGICAL ONCOLOGY
摘要:
信号调节蛋白 α (SIRPα) 是巨噬细胞上表达的免疫检查点分子,通过与肿瘤细胞上表达的 CD47 结合来抑制吞噬作用。 SIRPα作为癌症免疫治疗的新靶点受到越来越多的关注;然而,SIRPα在肺鳞状细胞癌(LUSC)中的表达和免疫功能仍不清楚。因此,本研究旨在确定 LUSC 中 SIRPα 表达的临床重要性,并探讨 SIRPα 表达升高的因素。 对 172 例患者手术切除的原发 LUSC 标本进行免疫组化评估肿瘤相关巨噬细胞 SIRPα 表达与临床病理特征的关系和临床结果。此外,我们分析了 SIRPα 表达与肿瘤浸润淋巴细胞和程序性细胞死亡配体 1 (PD-L1) 表达的关联。在体外,用细胞因子处理单核细胞,并通过流式细胞术评估SIRPα蛋白表达。SIRPα表达与临床病理因素没有差异。高 SIRPα 表达与 PD-L1 阳性表达以及高 CD8、PD-1 和 CD163 表达显着相关。 SIRPα 高表达组的无复发生存期 (RFS) 和总生存期 (OS) 显着缩短。多变量分析显示,SIRPα 高表达是 RFS 和 OS 的独立不良预后因素。单核细胞中 SIRPα 蛋白的表达通过 IFNγ 治疗上调。我们的分析表明,高 SIRPα 表达显着预测手术切除 LUSC 患者的不良预后。© 2024。外科肿瘤学会。
Signal-regulatory protein alpha (SIRPα) is an immune checkpoint molecule expressed on macrophages that functions to inhibit phagocytosis by binding to CD47 expressed on tumor cells. SIRPα has attracted increasing attention as a novel target for cancer immunotherapy; however, the expression and immune function of SIRPα in lung squamous cell carcinoma (LUSC) remain unclear. Therefore, this study aimed to identify the clinical importance of SIRPα expression in LUSC and to explore the factors that elevate SIRPα expression.Primary LUSC specimens surgically resected from 172 patients underwent immunohistochemical evaluation of the association of SIRPα expression on tumor-associated macrophages with clinicopathological features and clinical outcomes. Furthermore, we analyzed the association of SIRPα expression with tumor-infiltrating lymphocytes and the expression of programmed cell death ligand 1 (PD-L1). In vitro, monocytes were treated with cytokines, and SIRPα protein expression was assessed by flow cytometry.There were no differences in SIRPα expression and clinicopathological factors. High SIRPα expression was significantly associated with PD-L1-positive expression, and high CD8, PD-1, and CD163 expression. The high SIRPα expression group showed significantly shorter recurrence-free survival (RFS) and overall survival (OS). On multivariate analysis, high SIRPα expression was an independent poor prognostic factor for RFS and OS. The expression of SIRPα protein in monocytes was upregulated by treatment with IFNγ.Our analysis revealed that high SIRPα expression significantly predicts poor prognosis in patients with surgically resected LUSC.© 2024. Society of Surgical Oncology.