Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Sci Rep. 2019 Dec 27;9(1):20197. doi: 10.1038/s41598-019-56828-7.
With the increasing oncological potential of immunotherapy, several immune checkpoint modulators are being investigated. The value of immune markers, including programmed cell death ligand-1, programmed cell death-1 (PD-1), inducible co-stimulator (ICOS), lymphocyte activation gene-3, T-cell immunoglobulin, and mucin-dominant containing-3 (TIM-3), is not well known. Using tissue microarrays of 396 patients who underwent surgery for oesophageal squamous cell carcinoma (ESCC), infiltrated T-cell subsets (CD3, CD8, and Foxp3) and checkpoint protein expression were scored. With a median follow-up of 24.8 months, CD3 TIL subsets (50.0%) had longer median recurrence-free survival (RFS, 55.0 vs 21.4 months) and overall survival (OS, 77.7 vs 35.8 months). Patients with high ICOS expression (46.5%) had longer median RFS (53.9 vs 25.3 months) and OS (88.8 vs 36.9 months). For PD-1, RFS (hazard ratio [HR] 0.67) and OS (HR 0.66) were significantly longer in the high-expression group (45.2%). In the multivariate analysis, high TIM-3 expression (50.8%) had a significant relationship with shorter RFS (HR = 1.52) and OS (HR = 1.60). High CD3 TIL and T-cell ICOS expression were associated with favourable prognosis, whereas high TIM-3 expression suggested a poor prognosis. Our findings may confer new insights to improve ESCC outcomes beyond the application of PD-1 blockade.
随着免疫疗法在肿瘤学方面的潜力不断增加，几种免疫检查点调节剂正在被研究。包括程序性细胞死亡配体 1（PD-L1）、程序性细胞死亡蛋白 1（PD-1）、诱导共刺激分子（ICOS）、淋巴细胞激活基因 3（LAG-3）、T 细胞免疫球蛋白和粘蛋白-3（TIM-3）在内的免疫标志物的价值尚不清楚。本研究使用了 396 名接受食管鳞癌（ESCC）手术的患者的组织微阵列，对浸润性 T 细胞亚群（CD3、CD8 和 Foxp3）和检查点蛋白表达进行了评分。中位随访 24.8 个月后，CD3 TIL 亚群（50.0%）的无复发生存率（RFS，55.0 与 21.4 个月）和总生存率（OS，77.7 与 35.8 个月）更长。ICOS 高表达（46.5%）的患者的 RFS（风险比[HR]0.67）和 OS（HR 0.66）更长，中位时间分别为 53.9 与 25.3 个月和 88.8 与 36.9 个月。对于 PD-1，高表达组（45.2%）的 RFS（HR0.67）和 OS（HR0.66）显著更长。多变量分析显示，高 TIM-3 表达（50.8%）与较短的 RFS（HR1.52）和 OS（HR1.60）显著相关。高 CD3 TIL 和 T 细胞 ICOS 表达与良好的预后相关，而高 TIM-3 表达则提示预后不良。我们的研究结果可能为改善 ESCC 患者的预后提供新的思路，而不仅仅是应用 PD-1 阻断。
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