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.

中文翻译：

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乳腺癌中 PD-1/PD-L1 免疫检查点阻断的研究见解和致敏策略


靶向程序性细胞死亡 1 （PD-1） 和 PD-L1 免疫检查点的免疫疗法重塑了包括乳腺癌在内的多种癌症的治疗模式。PD-1/PD-L1 免疫检查点阻断 （ICB） 与化疗相结合在早期和转移性三阴性乳腺癌中均显示出有希望的疗效，尽管只有一部分患者经历了持久的反应。因此，识别反应者和优化免疫药物选择至关重要。PD-1/PD-L1 免疫疗法的有效性取决于肿瘤-内在因素和肿瘤微环境 （TME） 内的外源性细胞-细胞相互作用。本文系统总结了 ICBs 在乳腺癌中临床试验的主要发现，并探讨了 PD-L1 表达调控的机制。我们还强调了在确定 PD-1/PD-L1 治疗的潜在生物标志物方面的最新进展以及治疗后 TME 改变的新证据。其中，肿瘤浸润淋巴细胞的数量、免疫表型和空间分布是有前途的生物标志物。此外，我们探索了提高 ICB 在乳腺癌中的有效性的策略，旨在支持根据每位患者肿瘤的独特特征开发个性化治疗方法。