Gilmore Elaine, McCabe Nuala, Kennedy Richard D, Parkes Eileen E
Queen's University Belfast, Centre for Cancer Research and Cell Biology, 97 Lisburn Road, Belfast BT9 7AE, UK.
Almac Diagnostics, 20 Seagoe Road, Craigavon BT63 5QD, UK.
J Oncol. 2019 Jun 19;2019:4325105. doi: 10.1155/2019/4325105. eCollection 2019.
Historically the development of anticancer treatments has been focused on their effect on tumor cells alone. However, newer treatments have shifted attention to targets on immune cells, resulting in dramatic responses. The effect of DNA repair deficiency on the microenvironment remains an area of key interest. Moreover, established therapies such as DNA damaging treatments such as chemotherapy and PARP inhibitors further modify the tumor microenvironment. Here we describe DNA repair pathways in breast cancer and activation of innate immune pathways in DNA repair deficiency, in particular, the STING (STimulator of INterferon Genes) pathway. Breast tumors with DNA repair deficiency are associated with upregulation of immune checkpoints including PD-L1 (Programmed Death Ligand-1) and may represent a target population for single agent or combination immunotherapy treatment.
从历史上看，抗癌治疗的发展一直仅专注于其对肿瘤细胞的作用。然而，更新的治疗方法已将注意力转移到免疫细胞上的靶点，从而产生了显著的反应。DNA修复缺陷对微环境的影响仍然是一个关键的研究领域。此外，诸如化疗和PARP抑制剂等DNA损伤治疗等既定疗法会进一步改变肿瘤微环境。在这里，我们描述了乳腺癌中的DNA修复途径以及DNA修复缺陷时固有免疫途径的激活，特别是STING（干扰素基因刺激因子）途径。存在DNA修复缺陷的乳腺肿瘤与包括PD-L1（程序性死亡配体1）在内的免疫检查点上调有关，可能代表单药或联合免疫治疗的目标人群。
