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实体瘤中三级淋巴结构密度与免疫检查点抑制剂疗效的相关性：系统评价和荟萃分析。

Associations between tertiary lymphoid structure density and immune checkpoint inhibitor efficacy in solid tumors: systematic review and meta-analysis.

机构信息

Department of Thoracic Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.

出版信息

Front Immunol. 2024 Oct 31;15:1414884. doi: 10.3389/fimmu.2024.1414884. eCollection 2024.

DOI:10.3389/fimmu.2024.1414884
PMID:39544934
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11560435/
Abstract

BACKGROUND

Tertiary lymphoid structures (TLS) play a crucial role in tumor immunity, yet their relationship with the efficacy of immune checkpoint inhibitors (ICI) in cancer therapy is not fully understood. This study aims to systematically evaluate how TLS density influences treatment outcomes in cancer patients receiving ICI therapy.

METHODS

The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for eligible studies published before January 22, 2024. Our analysis encompassed odds ratios (ORs) for response rates (RRs) and hazard ratios (HRs) for progression-free survival (PFS), each with their respective 95% confidence intervals (CIs).

RESULTS

Our meta-analysis, including 19 clinical trials with 1,752 patients, identified a strong correlation between high TLS density and increased RR to ICIs (OR= 2.99, 95% CI: 2.14-4.18, < 0.001). Furthermore, a higher TLS density was associated with prolonged PFS (HR=0.75, 95% CI: 0.63-0.88, < 0.001). Specifically, in the context of non-small cell lung cancer (NSCLC), breast cancer (BC), renal cell carcinoma (RCC), esophageal cancer (EC), and urothelial carcinoma (UC), a significant relationship was observed between high TLS density and better ICI efficacy. Publication bias did not affect the integrity of our conclusions. Sensitivity analysis further reinforced the reliability of our aggregated outcomes.

CONCLUSION

Our meta-analysis underscores the predictive role of TLS density in determining the RR and PFS among cancer patients undergoing ICI therapy. These results highlight the prognostic significance of TLS, suggesting its potential as a biomarker for guiding treatment decisions, even in tumor types traditionally considered ICI-resistant. Clinicians are recommended to assess TLS density as a part of patient evaluation to optimize ICI therapy initiation.

SYSTEMATIC REVIEW REGISTRATION

https://www.crd.york.ac.uk/prospero/, identifier CRD42023439875.

摘要

背景

三级淋巴结构 (TLS) 在肿瘤免疫中起着至关重要的作用，但它们与癌症治疗中免疫检查点抑制剂 (ICI) 疗效的关系尚未完全阐明。本研究旨在系统评估 TLS 密度如何影响接受 ICI 治疗的癌症患者的治疗结果。

方法

检索了 PubMed、Embase、Cochrane 图书馆和 Web of Science 数据库，以获取截至 2024 年 1 月 22 日之前发表的合格研究。我们的分析包括反应率 (RR) 的优势比 (OR) 和无进展生存期 (PFS) 的风险比 (HR)，每个都有各自的 95%置信区间 (CI)。

结果

我们的荟萃分析包括 19 项临床试验和 1752 名患者，结果表明 TLS 密度与 ICI 治疗的 RR 增加之间存在很强的相关性（OR=2.99，95%CI：2.14-4.18，<0.001）。此外，较高的 TLS 密度与 PFS 延长相关（HR=0.75，95%CI：0.63-0.88，<0.001）。具体而言，在非小细胞肺癌 (NSCLC)、乳腺癌 (BC)、肾细胞癌 (RCC)、食管癌 (EC) 和膀胱癌 (UC) 中，TLS 密度与 ICI 疗效较好之间存在显著关系。发表偏倚并未影响我们结论的完整性。敏感性分析进一步加强了我们汇总结果的可靠性。

结论

我们的荟萃分析强调了 TLS 密度在确定接受 ICI 治疗的癌症患者 RR 和 PFS 中的预测作用。这些结果突出了 TLS 的预后意义，表明其作为指导治疗决策的生物标志物的潜力，即使在传统上被认为对 ICI 耐药的肿瘤类型中也是如此。建议临床医生将 TLS 密度评估作为患者评估的一部分，以优化 ICI 治疗的启动。

系统评价注册

https://www.crd.york.ac.uk/prospero/，标识符 CRD42023439875。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/11560435/abe91191164b/fimmu-15-1414884-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/11560435/1d596438e8ac/fimmu-15-1414884-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/11560435/ae6cb0e6f920/fimmu-15-1414884-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/11560435/1fb5d12c3577/fimmu-15-1414884-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/11560435/f705032c1018/fimmu-15-1414884-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/11560435/5335f3c49456/fimmu-15-1414884-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/11560435/abe91191164b/fimmu-15-1414884-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/11560435/1d596438e8ac/fimmu-15-1414884-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/11560435/ae6cb0e6f920/fimmu-15-1414884-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/11560435/1fb5d12c3577/fimmu-15-1414884-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/11560435/f705032c1018/fimmu-15-1414884-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/11560435/5335f3c49456/fimmu-15-1414884-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f6/11560435/abe91191164b/fimmu-15-1414884-g006.jpg

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