Based on its known role in mediating tumor progression and the correlation with poor response to chemotherapy, we hypothesized that blocking interleukin-17A (IL-17A) by anti-IL-17 monoclonal antibodies might have the ability to suppress programmed death-ligand-1 (PD-L1) and to modulate the expression and function of myeloid-derived suppressor cells (MDSCs) in BC microenvironment. We also compared the apoptotic activity of anti-IL-17 with those acquired from our previous work on monoclonal antibodies against IL-6. The influence of anti-IL-17 was investigated in two doses on localized freshly resected tissues from 50 patients with BC. Results revealed increased IL-17A in BC tumor tissues versus surrounding tissues. Additionally, PD-L1 expression was inhibited in cultures treated with both doses of anti-IL-17. Frequencies of MDSCs were reduced in those cultures with anti-IL-17 with reduced suppressive activity. The induced apoptosis in the tumor cells was significantly increased. Anti-IL-17 antibodies effect was related to late stages, vascular metastasis, and hormonal status. Results of the current work suggest a promising role for anti-IL-17 monoclonal antibodies in enhancement of anti-tumor immunological activity in BC, potentially involving suppression of immune checkpoint PD-L1 and MDSCs inhibition with a marked response in aggressive disease.

基于其在介导肿瘤进展中的已知作用以及与对化疗反应不佳的相关性，我们假设通过抗 IL-17 单克隆抗体阻断白介素 17A (IL-17A) 可能具有抑制程序性死亡配体 1 的能力(PD-L1) 并调节骨髓源性抑制细胞 (MDSC) 在 BC 微环境中的表达和功能。我们还将抗 IL-17 的细胞凋亡活性与我们之前对 IL-6 单克隆抗体的研究中获得的细胞凋亡活性进行了比较。研究了两剂抗 IL-17 对来自 50 名 BC 患者的局部新鲜切除组织的影响。结果显示与周围组织相比，BC 肿瘤组织中的 IL-17A 增加。此外，在用两种剂量的抗 IL-17 处理的培养物中，PD-L1 的表达都受到抑制。在抑制活性降低的抗 IL-17 培养物中 MDSC 的频率降低。诱导的肿瘤细胞凋亡明显增加。抗 IL-17 抗体的作用与晚期、血管转移和激素状态有关。目前的工作结果表明，抗 IL-17 单克隆抗体在增强 BC 中的抗肿瘤免疫活性方面具有有希望的作用，可能涉及抑制免疫检查点 PD-L1 和 MDSCs 抑制，并在侵袭性疾病中产生显着反应。