Department of Pathology, 89674Zhongnan Hospital of Wuhan University, Wuhan, China.
Technol Cancer Res Treat. 2021 Jan-Dec;20:15330338211034265. doi: 10.1177/15330338211034265.
To evaluate the prognostic value of tumor infiltrating lymphocytes (TILs) in nasopharyngeal carcinoma (NPC) patients.
Meta-analysis was performed on eligible studies that was identified by systematic searching of Google scholar, MEDLINE, CNKI, Scopus, PubMed, PMC, Embase and Web of Science databases. The study protocol was registered in International Platform of Registered Systematic Review and Meta-Analysis Protocols-INPLASY (registration number: INPLASY202160014). Databases were searched from inception to January 20, 2020 to identify eligible studies. Those studies that evaluated survival in the form of hazard ratio (HR) in TILs of NPC patients was analyzed. All statistical analysis was performed by using STATA version 16.0 software.
Fourteen studies with a total of 3025 patients was analyzed. The pooled result showed that high TILs was significantly associated with favorable overall survival (OS) (HR = 0.55; 95%CI = 0.39-0.77; = 0.001) and disease free survival (DFS) (HR = 0.60; 95%CI = 0.44-0.81; = 0.04). Interestingly, high intratumoral TILs had relatively better OS (HR = 0.45; 95%CI = 0.35-0.58; = 0.006) than stromal TILs (HR = 0.59; 95%CI = 0.36-0.97; = 0.03). Moreover, an increased level of CD4+ cells infiltration was correlated with favorable OS (HR = 0.4; 95%CI = 0.18-0.85; = 0.01). CD3+, CD8+ and FoxP3+ lymphocyte's better prognosis was not statistically significant for OS ( = 0.09; = 0.07; = 0.52) and for DFS ( = 0.13; = 0.29) respectively. However, subgroup analysis of intratumoral CD3+ (HR = 0.48; 95%CI = 0.33-0.70; = 0.05) and intratumoral CD8+ (HR = 0.32; 95%CI = 0.16-0.62; = 0.001) was significantly associated with improved OS, but not significant in stromal CD3+ (HR = 0.66; 95%CI = 0.20-2.20; = 0.62).
TILs were variably correlated with better prognosis depending on their microanatomic location and subset of TILs in NPC patients. CD4+, intratumoral CD3+ and intratumoral CD8+ lymphocytes could predict favorable patient outcome which suggest that their role in mediating antitumor immune response could potentially be exploited in the treatment of NPC patients. Future large study on the prognostic value of microanatomic location of TILs is needed for confirmation.
评估肿瘤浸润淋巴细胞(TILs)在鼻咽癌(NPC)患者中的预后价值。
通过系统搜索 Google Scholar、MEDLINE、CNKI、Scopus、PubMed、PMC、Embase 和 Web of Science 数据库,对符合条件的研究进行荟萃分析。该研究方案已在国际注册系统评价和荟萃分析方案平台-INPLASY(注册号:INPLASY202160014)上注册。从数据库建立到 2020 年 1 月 20 日检索了符合条件的研究。分析了以 NPC 患者 TILs 形式评估生存的研究,评估了危险比(HR)。所有统计分析均使用 STATA 版本 16.0 软件进行。
分析了 14 项共 3025 例患者的研究。汇总结果表明,高 TILs 与总生存(OS)(HR = 0.55;95%CI = 0.39-0.77; = 0.001)和无病生存(DFS)(HR = 0.60;95%CI = 0.44-0.81; = 0.04)显著相关。有趣的是,高肿瘤内 TILs 与 OS (HR = 0.45;95%CI = 0.35-0.58; = 0.006)相比,间质 TILs 具有更好的 OS(HR = 0.59;95%CI = 0.36-0.97; = 0.03)。此外,CD4+细胞浸润水平升高与 OS (HR = 0.4;95%CI = 0.18-0.85; = 0.01)相关。CD3+、CD8+和 FoxP3+淋巴细胞的预后较好,OS( = 0.09; = 0.07; = 0.52)和 DFS( = 0.13; = 0.29)的差异无统计学意义。然而,肿瘤内 CD3+(HR = 0.48;95%CI = 0.33-0.70; = 0.05)和肿瘤内 CD8+(HR = 0.32;95%CI = 0.16-0.62; = 0.001)的亚组分析与 OS 显著相关,但间质 CD3+(HR = 0.66;95%CI = 0.20-2.20; = 0.62)的差异无统计学意义。
TILs 的预后相关性因微解剖位置和 NPC 患者 TILs 的亚群而异。CD4+、肿瘤内 CD3+和肿瘤内 CD8+淋巴细胞可预测患者的良好预后,提示其在介导抗肿瘤免疫反应中的作用可能被利用于 NPC 患者的治疗。需要进一步的大样本研究来证实 TILs 微解剖位置的预后价值。