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PD-1/PD-L1 免疫检查点阻断在乳腺癌中的研究见解与增敏策略

英文原题:PD-1/PD-L1 immune checkpoint blockade in breast cancer: research insights and sensitization strategies.

查看英文原题

PD-1/PD-L1 immune checkpoint blockade in breast cancer: research insights and sensitization strategies.

PubMed 2024/11/29(内容时间) Mol Cancer Q1 · IF 42.2(JCR 2025)

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中文摘要

靶向程序性细胞死亡-1(PD-1)和PD-L1免疫检查点的免疫治疗已重塑了包括乳腺癌在内的多种癌症的治疗格局。将PD-1/PD-L1免疫检查点阻断(ICB)与化疗联合,在早期和转移性三阴性乳腺癌中均显示出有前景的疗效,尽管仅有一部分患者能获得持久缓解。因此,识别应答者和优化免疫药物选择至关重要。PD-1/PD-L1免疫治疗的有效性取决于肿瘤内在因素以及肿瘤微环境(TME)中的外在细胞-细胞相互作用。本综述系统总结了ICB在乳腺癌临床试验中的关键发现,并探讨了PD-L1表达调控的机制。我们还重点介绍了识别PD-1/PD-L1治疗潜在生物标志物的最新进展,以及治疗后TME改变的新兴证据。其中,TIL(肿瘤浸润淋巴细胞)的数量、免疫表型和空间分布作为有前景的生物标志物尤为突出。此外,我们探讨了增强ICB在乳腺癌中有效性的策略,旨在支持针对每位患者肿瘤独特特征制定个性化治疗方案的开发。

展开英文摘要原文

Immunotherapy targeting programmed cell death-1 (PD-1) and PD-L1 immune checkpoints has reshaped treatment paradigms across several cancers, including breast cancer. Combining PD-1/PD-L1 immune checkpoint blockade (ICB) with chemotherapy has shown promising efficacy in both early and metastatic triple-negative breast cancer, although only a subset of patients experiences durable responses.

Identifying responders and optimizing immune drug selection are therefore critical. The effectiveness of PD-1/PD-L1 immunotherapy depends on both tumor-intrinsic factors and the extrinsic cell-cell interactions within the tumor microenvironment (TME). This review systematically summarizes the key findings from clinical trials of ICBs in breast cancer and examines the mechanisms underlying PD-L1 expression regulation.

We also highlight recent advances in identifying potential biomarkers for PD-1/PD-L1 therapy and emerging evidence of TME alterations following treatment. Among these, the quantity, immunophenotype, and spatial distribution of tumor-infiltrating lymphocytes stand out as promising biomarkers.

Additionally, we explore strategies to enhance the effectiveness of ICBs in breast cancer, aiming to support the development of personalized treatment approaches tailored to the unique characteristics of each patient's tumor.

论文信息

作者
Jin M、Fang J、Peng J、Wang X、Xing P、Jia K、Hu J、Wang D
第一作者单位
Department of Breast Surgery (Surgical Oncology), Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang, China.China
通讯作者单位
Department of Breast Surgery (Surgical Oncology), Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang, China. chenzhigang@zju.edu.cn.China
文献类型
系统综述 · 非美国政府资助研究
期刊
Molecular cancer2024 Nov 29
原文标识
PubMed 39614285 · DOI 10.1186/s12943-024-02176-8