a Centre de recherche en Cancérologie de Marseille, INSERM U1068, CNRS U7258 , Aix Marseille Université, Institut Paoli - Calmettes , Marseille , France.
Expert Opin Ther Targets. 2018 Apr;22(4):343-351. doi: 10.1080/14728222.2018.1444753. Epub 2018 Mar 1.
The recent success of checkpoint-inhibitors in cancer treatment paved the way for the development of new strategies of agonist and antagonist agents against B7 superfamily members. Inducible Co-Stimulator (ICOS), a co-stimulatory receptor for T-cell enhancement, arouses interest. Areas covered: We performed an extensive literature search with PUBMED using the keywords 'ICOS' and 'cancer' to discuss its involvement in oncogenesis, its expression in different malignancies, and its targeting in relevant preclinical studies. We also searched the Clinicaltrials.gov database for recent updates on early phase clinical trials. Expert opinion: ICOS/ICOSL axis has a dual effect and might participate in anti-tumour T cell response as well as a pro-tumour response due to its connection with regulatory T-cells (Tregs) suppressive activity. Therefore, both antagonist and agonist antibodies might be of interest in the targeting ICOS/ICOSL pathway for cancer treatment. In preclinical studies, ICOS agonist monoclonal antibodies (mAbs) have shown to potentiate the effect of inhibitory checkpoint blockade. In contrast, antagonistic anti-ICOS mAbs could not only inhibit lymphoid tumour cells expressing ICOS, but also dampen immunosuppressive Tregs. Two agonist and one antagonist mAbs are evaluated in phase I/II trials. Efficacy, safety, and combination strategies with anti-ICOS agonist or antagonist have yet to be specified.
近年来，检查点抑制剂在癌症治疗方面的成功为开发针对 B7 超家族成员的激动剂和拮抗剂新策略铺平了道路。诱导共刺激因子（ICOS）是 T 细胞增强的共刺激受体，引起了人们的兴趣。
我们使用 PUBMED 进行了广泛的文献检索，使用关键词“ICOS”和“cancer”来讨论其在肿瘤发生中的作用、在不同恶性肿瘤中的表达以及在相关临床前研究中的靶向作用。我们还在 Clinicaltrials.gov 数据库中搜索了早期临床试验的最新更新。
ICOS/ICOSL 轴具有双重作用，由于其与调节性 T 细胞（Tregs）的抑制活性有关，因此可能参与抗肿瘤 T 细胞反应以及促肿瘤反应。因此，针对 ICOS/ICOSL 通路的拮抗剂和激动剂抗体可能都对癌症治疗有意义。在临床前研究中，ICOS 激动性单克隆抗体（mAb）已被证明可以增强抑制性检查点阻断的效果。相比之下，拮抗性抗 ICOS mAb 不仅可以抑制表达 ICOS 的淋巴样肿瘤细胞，还可以抑制免疫抑制性 Tregs。目前正在评估两种激动剂和一种拮抗剂 mAb 的 I 期/II 期临床试验。疗效、安全性以及与激动剂或拮抗剂抗 ICOS 的联合策略仍有待确定。
