三阴性乳腺癌患者肿瘤浸润淋巴细胞的预后价值：系统评价和荟萃分析。
Prognostic value of tumor-infiltrating lymphocytes in patients with triple-negative breast cancer: a systematic review and meta-analysis.
机构信息
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center for Digestive Diseases, 95 Yong-an Road, Beijing, 100050, China.
出版信息
BMC Cancer. 2020 Mar 4;20(1):179. doi: 10.1186/s12885-020-6668-z.
BACKGROUND
The objective of this systematic review and meta-analysis was to determine the prognostic value of total tumor-infiltrating lymphocytes (TILs) and subtypes of TILs (CD4, CD8, and FOXP3) in triple-negative breast cancer (TNBC).
METHODS
A systematic search of the MEDLINE, EMBASE, and Web of Science databases was conducted to identified eligible articles published before August 2019. Study screening, data extraction, and risk of bias assessment were performed by two independent reviewers. Risk of bias on the study level was assessed using the ROBINS I tool and Quality in Prognosis Studies (QUIPS) tool. We performed a meta-analysis to obtain a pooled estimate of the prognostic role of TILs using Review Manager 5.3.
RESULTS
In total, 37 studies were included in the final analysis. Compared to TNBC patients with low TIL levels, TNBC patients with high TIL levels showed a higher rate of pathological complete response (pCR) to treatment (odds ratio [OR] 2.14, 95% confidence interval [CI] 1.43-3.19). With each 10% increase in percentage of TILs, patients with TNBC had an increased pCR (OR 1.09, 95% CI 1.02-1.16). Compared to TNBC patients with low TIL levels, patients with high TIL levels had better overall survival (OS; hazard ratio [HR] 0.58, 95% CI 0.48-0.71) and disease-free survival (DFS; HR 0.66, 95% CI 0.57-0.76). Additionally, with a continuous increase in TIL levels, patients with TNBC had improved OS (HR 0.90, 95% CI 0.87-0.93) and DFS (HR 0.92, 95% CI 0.90-0.95). A high CD4 TIL level was associated with better OS (HR 0.49, 95% CI 0.32-0.76) and DFS (HR 0.54, 95% CI 0.36-0.80). A high CD8 TIL level was associated better DFS only (HR 0.55, 95% CI 0.38-0.81), as no statistical association was found with OS (HR 0.70, 95% CI 0.46-1.06). A high FOXP3 TIL level also was associated with only DFS (HR 0.50, 95% CI 0.33-0.75) and not OS (HR 1.28, 95% CI 0.24-6.88).
CONCLUSIONS
TNBC with a high level of TILs showed better short-term and long-term prognoses. High levels of specific phenotypes of TILs (CD4, CD8, and FOXP3) were predictive of a positive long-term prognosis for TNBC.
背景
本系统评价和荟萃分析的目的是确定总肿瘤浸润淋巴细胞（TILs）及其亚型（CD4、CD8 和 FOXP3）在三阴性乳腺癌（TNBC）中的预后价值。
方法
对 MEDLINE、EMBASE 和 Web of Science 数据库进行系统检索，以确定截至 2019 年 8 月之前发表的合格文章。两名独立评审员进行了研究筛选、数据提取和偏倚风险评估。使用 ROBINS I 工具和预后研究质量（QUIPS）工具评估研究层面的偏倚风险。我们使用 Review Manager 5.3 进行荟萃分析，以获得 TILs 预后作用的汇总估计值。
结果
共有 37 项研究纳入最终分析。与 TIL 水平低的 TNBC 患者相比，TIL 水平高的 TNBC 患者对治疗的病理完全缓解（pCR）率更高（比值比 [OR] 2.14，95%置信区间 [CI] 1.43-3.19）。TIL 百分比每增加 10%，TNBC 患者的 pCR 增加（OR 1.09，95%CI 1.02-1.16）。与 TIL 水平低的 TNBC 患者相比，TIL 水平高的患者总生存（OS；风险比 [HR] 0.58，95%CI 0.48-0.71）和无病生存（DFS；HR 0.66，95%CI 0.57-0.76）更好。此外，随着 TIL 水平的连续升高，TNBC 患者的 OS（HR 0.90，95%CI 0.87-0.93）和 DFS（HR 0.92，95%CI 0.90-0.95）得到改善。高 CD4 TIL 水平与更好的 OS（HR 0.49，95%CI 0.32-0.76）和 DFS（HR 0.54，95%CI 0.36-0.80）相关。高 CD8 TIL 水平仅与更好的 DFS 相关（HR 0.55，95%CI 0.38-0.81），与 OS 无统计学关联（HR 0.70，95%CI 0.46-1.06）。高 FOXP3 TIL 水平也仅与 DFS 相关（HR 0.50，95%CI 0.33-0.75），而与 OS 无关（HR 1.28，95%CI 0.24-6.88）。
结论
TIL 水平高的 TNBC 患者短期和长期预后较好。TIL 特定表型（CD4、CD8 和 FOXP3）水平较高预示着 TNBC 的长期预后良好。
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