Bedognetti Davide, Maccalli Cristina, Bader Salha B J Al, Marincola Francesco M, Seliger Barbara
Tumor Biology, Immunology, and Therapy Section, Division of Translational Medicine, Sidra Medical and Research Center, Doha, Qatar.
National Center for Cancer Care and Research (NCCCR), and Hamad General Hospital, Doha, Qatar.
Breast Care (Basel). 2016 Apr;11(2):108-15. doi: 10.1159/000445335. Epub 2016 Apr 26.
Immune checkpoints are crucial for the maintenance of self-tolerance and for the modulation of immune responses in order to minimize tissue damage. Tumor cells take advantage of these mechanisms to evade immune recognition. A significant proportion of tumors, including breast cancers, can express co-inhibitory molecules that are important formediating the escape from T cell-mediated immune surveillance. The interaction of inhibitory receptors with their ligands can be blocked by specific molecules. Monoclonal antibodies (mAbs) directed against the cytotoxic T lymphocyte-associated antigen-4 (CTLA4) and, more recently, against the programmed cell death protein 1 (PD1), have been approved for the therapy of melanoma (anti-CTLA4 and anti-PD1 mAbs) and non-small cell lung cancer (anti-PD1 mAbs). Moreover, inhibition of PD1 signaling has shown extremely promising signs of activity in breast cancer. An increasing number of molecules directed against other immune checkpoints are currently under clinical development. In this review, we summarize the evidence supporting the implementation of checkpoint inhibition in breast cancer by reviewing in detail data on PD-L1 expression and its regulation. In addition, opportunities to boost anti-tumor immunity in breast cancer with checkpoint inhibitor-based immunotherapies alone and in combination with other treatment options will be discussed.
免疫检查点对于维持自身耐受性以及调节免疫反应以尽量减少组织损伤至关重要。肿瘤细胞利用这些机制逃避免疫识别。包括乳腺癌在内的很大一部分肿瘤能够表达共抑制分子，这些分子对于介导从T细胞介导的免疫监视中逃逸很重要。抑制性受体与其配体的相互作用可被特定分子阻断。针对细胞毒性T淋巴细胞相关抗原4（CTLA4）以及最近针对程序性细胞死亡蛋白1（PD1）的单克隆抗体（mAb）已被批准用于治疗黑色素瘤（抗CTLA4和抗PD1 mAb）和非小细胞肺癌（抗PD1 mAb）。此外，抑制PD1信号传导在乳腺癌中已显示出极具前景的活性迹象。目前越来越多针对其他免疫检查点的分子正处于临床开发阶段。在本综述中，我们通过详细回顾关于PD-L1表达及其调节的数据，总结支持在乳腺癌中实施检查点抑制的证据。此外，还将讨论单独使用基于检查点抑制剂的免疫疗法以及与其他治疗方案联合使用来增强乳腺癌抗肿瘤免疫力的机会。
