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LAG-3(+)TIL(肿瘤浸润淋巴细胞)改善了三阴性乳腺癌患者的总生存期

英文原题:LAG-3(+) tumor-infiltrating lymphocytes ameliorates overall survival in triple-negative breast cancer patients.

查看英文原题

LAG-3(+) tumor-infiltrating lymphocytes ameliorates overall survival in triple-negative breast cancer patients.

PubMed 2023/01/24(内容时间) Front Oncol Q2 · IF 3.4(JCR 2025)

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研究概要

LAG-3+淋巴细胞的浸润改善了 TNBC 和 Her2 阳性 BC 的 OS,提示其是一个有价值的预后生物标志物,而抗 LAG-3 拮抗剂的应用可能并非人类 BC 尤其是 TNBC 的有前景的治疗策略。

研究思路结论见上方概要

免疫检查点分子淋巴细胞活化基因-3(LAG-3)表达于活跃的淋巴细胞上,已被证明与多种实体瘤中的免疫抑制和癌症进展相关。然而,LAG-3+淋巴细胞在人乳腺癌(BC)中的作用仍无定论。因此,我们进行了一项meta分析,以阐明这些细胞在BC预后预测中的作用。

我们检索了PubMed、Embase和EBSCO,以识别评估BC患者中LAG-3+淋巴细胞浸润与总生存期(OS)和/或无病生存期(DFS)关联的研究,然后使用STATA 12.0合并提取的数据。

本meta分析纳入了8项已发表的研究,涉及5,859例BC患者。我们注意到,大量LAG-3+TIL(肿瘤浸润淋巴细胞)与BC患者的OS和DFS无明显相关性。引人注目的是,在基于BC分子分型的分层分析中,LAG-3+淋巴细胞浸润与三阴性乳腺癌(TNBC)中更好的OS显著相关,而非DFS,而在Her2阳性BC中,其对OS和DFS均无显著影响。然而,这些淋巴细胞密度增加提示Her2阳性BC中OS有改善趋势。此外,我们发现,当采用免疫组织化学(IHC)检测时,LAG-3+淋巴细胞浸润也与Her2阳性BC患者OS延长显著相关。此外,这些淋巴细胞数量升高与病理完全缓解率或临床病理特征(包括淋巴结转移)无关。

展开英文摘要原文

Immune checkpoint molecule lymphocyte-activating gene-3 (LAG-3), which is expressed on active lymphocytes, has proven to be associated with immunosuppression and cancer progression in a variety of solid tumors. However, the role of LAG-3 + lymphocytes in human breast cancer (BC) is still not conclusive. We therefore performed a meta-analysis to clarify the role of these cells in prognosis prediction for BC.

We searched PubMed, Embase, and EBSCO to identify the studies evaluating the association of LAG-3 + lymphocyte infiltration and overall survival (OS) and/or disease-free survival (DFS) in BC patients, then combined extracted data with STATA 12.0.

Eight published studies involving 5,859 BC patients were incorporated into this meta-analysis. We noted that a high number of LAG-3 + tumor-infiltrating lymphocytes were not appreciably associated with OS and DFS in BC patients. Strikingly, in stratified analyses based on the molecular type of BC, LAG-3 + lymphocyte infiltration was remarkably associated with better OS rather than DFS in triple-negative breast cancer (TNBC), whereas it significantly influenced neither OS nor DFS in Her2-positive BC. However, an increased density of these lymphocytes indicated a trend for better OS in Her2-positive BC. In addition, we found that LAG-3 + lymphocyte infiltration was also remarkably associated with prolonged OS in Her2-positive BC patients when they were measured by immunohistochemistry (IHC). In addition, an elevated number of these lymphocytes did not correlate with pathological complete response rate or clinicopathological features including lymph node metastasis.

The infiltration of LAG-3 + lymphocytes ameliorates OS in TNBC and Her2-positive BC, implicating that it is a valuable prognostic biomarker, and applications of anti-LAG-3 antagonists may possibly be not a promising therapeutic strategy for human BC especially for TNBC.

论文信息

作者
Hu G、Wang S、Wang S、Ding Q、Huang L
单位
Department of General Surgery (Breast and Thyroid Surgery), Shaoxing People's Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing, Zhejiang, China.China
文献类型
系统综述
期刊
Frontiers in oncology2022
原文标识
PubMed 36761428 · DOI 10.3389/fonc.2022.986903