Upregulation of inhibitory immune checkpoints is critical for the control of T-cell activation in order to prevent autoimmunity and tissue damage. It is now clear that tumors can hijack immune checkpoint mechanisms as protection against the anticancer T-cell response. Blockade of the PD-1/PD-L1 immune checkpoint pathway has created a revolution in the treatment of melanoma, lung cancer and several other cancer types. In metastatic breast cancer patients, the response rates to PD-1 blocking antibodies are modest (4%–25%), but durable responses are seen [1–7]. Given that the majority of patients do not have clinical benefit, there is an urgent need to improve immunotherapy for breast cancer patients. This optimization is not a paved road and requires the integration of different parallel approaches, such as the search for predictive biomarkers [8], combination treatment with conventional therapies [9, 10], strategies to convert cold tumors into hot tumors [4, 11] and development of novel immunomodulatory compounds.

中文翻译：

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LAG-3：释放乳腺癌的另一个障碍？

为了防止自身免疫和组织损伤，抑制性免疫检查点的上调对于控制T细胞活化至关重要。现在清楚的是，肿瘤可以劫持免疫检查点机制作为对抗癌T细胞反应的保护。PD-1 / PD-L1免疫检查点途径的阻断在黑色素瘤，肺癌和其他几种癌症类型的治疗方面掀起了一场革命。在转移性乳腺癌患者中，对PD-1阻断抗体的应答率不高（4％–25％），但观察到持久应答[1-7]。鉴于大多数患者没有临床益处，因此迫切需要改善针对乳腺癌患者的免疫疗法。这种优化并非铺平道路，需要整合不同的并行方法，例如寻找预测性生物标志物[8]，