Department of Neurosurgery, The First Hospital of China Medical University, No. 155 North Nanjing Street, Heping District, Shenyang, 110001, China.
Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai, 200080, China.
Cancer Immunol Immunother. 2019 Jul;68(7):1157-1169. doi: 10.1007/s00262-019-02349-1. Epub 2019 Jun 13.
Chordoma is difficult to eradicate due to high local recurrence rates. The immune microenvironment is closely associated with tumor prognosis; however, its role in skull base chordoma is unknown. The expression of Galectin-9 (Gal9) and tumor-infiltrating lymphocyte (TIL) markers was assessed by immunohistochemistry. Kaplan-Meier and multivariate Cox analyses were used to assessing local recurrence-free survival (LRFS) and overall survival (OS) of patients. MiR-455-5p was identified as a regulator of Gal9 expression. Immunopositivity for Gal9 was associated with tumor invasion (p = 0.019), Karnofsky performance status (KPS) score (p = 0.017), and total TIL count (p < 0.001); downregulation of miR-455-5p was correlated with tumor invasion (p = 0.017) and poor prognosis; and the T-cell immunoglobulin and mucin-domain 3 (TIM3) TIL count was associated with chordoma invasion (p = 0.010) and KPS score (p = 0.037). Furthermore, multivariate analysis indicated that only TIM3 TIL density was an independent prognostic factor for LRFS (p = 0.010) and OS (p = 0.016). These results can be used to predict clinical outcome and provide a basis for immune therapy in skull base chordoma patients.
软骨肉瘤由于局部复发率高而难以根除。免疫微环境与肿瘤预后密切相关,但在颅底软骨肉瘤中的作用尚不清楚。采用免疫组织化学法检测半乳糖凝集素-9(Gal9)和肿瘤浸润淋巴细胞(TIL)标志物的表达。采用 Kaplan-Meier 和多变量 Cox 分析评估患者的局部无复发生存率(LRFS)和总生存率(OS)。鉴定 miR-455-5p 为 Gal9 表达的调节剂。Gal9 免疫阳性与肿瘤侵袭(p=0.019)、卡氏功能状态(KPS)评分(p=0.017)和总 TIL 计数(p<0.001)相关;miR-455-5p 下调与肿瘤侵袭(p=0.017)和不良预后相关;T 细胞免疫球蛋白和粘蛋白结构域 3(TIM3)TIL 计数与软骨肉瘤侵袭(p=0.010)和 KPS 评分(p=0.037)相关。此外,多变量分析表明,只有 TIM3 TIL 密度是 LRFS(p=0.010)和 OS(p=0.016)的独立预后因素。这些结果可用于预测临床结果,并为颅底软骨肉瘤患者的免疫治疗提供依据。