Department of Molecular Medicine, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, Italy.
Int J Mol Sci. 2023 Aug 19;24(16):12958. doi: 10.3390/ijms241612958.
CD155, also known as the poliovirus receptor, is an adhesion molecule often overexpressed in tumors of different origins where it promotes cell migration and proliferation. In addition to this pro-tumorigenic function, CD155 plays an immunomodulatory role during tumor progression since it is a ligand for both the activating receptor DNAM-1 and the inhibitory receptor TIGIT, expressed on cytotoxic innate and adaptative lymphocytes. DNAM-1 is a well-recognized receptor involved in anti-tumor immune surveillance. However, in advanced tumor stages, TIGIT is up-regulated and acts as an immune checkpoint receptor, counterbalancing DNAM-1-mediated cancer cell clearance. Pre-clinical studies have proposed the direct targeting of CD155 on tumor cells as well as the enhancement of DNAM-1-mediated anti-tumor functions as promising therapeutic approaches. Moreover, immunotherapeutic use of anti-TIGIT blocking antibody alone or in combined therapy has already been included in clinical trials. The aim of this review is to summarize all these potential therapies, highlighting the still controversial role of CD155 during tumor progression.
CD155，也被称为脊髓灰质炎病毒受体，是一种黏附分子，常过度表达于不同来源的肿瘤中，促进细胞迁移和增殖。除了促进肿瘤发生的功能外，CD155 在肿瘤进展过程中还发挥免疫调节作用，因为它是激活受体 DNAM-1 和抑制性受体 TIGIT 的配体，而这两种受体均表达于细胞毒性先天和适应性淋巴细胞上。DNAM-1 是一种公认的参与抗肿瘤免疫监视的受体。然而，在晚期肿瘤阶段，TIGIT 上调并作为免疫检查点受体发挥作用，抵消了 DNAM-1 介导的癌细胞清除作用。临床前研究提出了直接针对肿瘤细胞上的 CD155 以及增强 DNAM-1 介导的抗肿瘤功能作为有前途的治疗方法。此外，单独使用或联合治疗的抗 TIGIT 阻断抗体的免疫治疗已被纳入临床试验。本综述的目的是总结所有这些潜在的治疗方法，强调 CD155 在肿瘤进展过程中仍存在争议的作用。
