RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The Nectin family ligands, PVRL2 and PVR, in cancer immunology and immunotherapy.
The Nectin family ligands, PVRL2 and PVR, in cancer immunology and immunotherapy.
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近年来,免疫治疗已成为癌症治疗的重要组成部分。然而,其在多种癌症类型中的疗效仍然有限,凸显了尚未满足的临床需求。脊髓灰质炎病毒受体相关2(PVRL2)和脊髓灰质炎病毒受体(PVR)是Nectin及Nectin样分子家族的成员,以细胞间黏附分子的作用而著称。随着免疫治疗的发展,它们作为免疫检查点分子参与肿瘤免疫机制的问题引起了广泛关注。PVRL2和PVR主要表达于肿瘤细胞和抗原提呈细胞,分别与主要存在于T细胞和NK细胞上的PVRIG和TIGIT结合,从而抑制抗肿瘤免疫。
值得注意的是,卵巢癌和子宫内膜癌等妇科肿瘤中PVRL2和PVR呈高表达水平,在多种其他实体瘤和血液系统肿瘤中也观察到类似趋势。靶向这些免疫检查点通路为治疗提供了有前景的途径,并可能与现有治疗联合应用。
然而,涉及这些结合的免疫调节机制,即所谓的DNAM-1轴,十分复杂,理解该机制对于开发新型疗法至关重要。本文全面综述了以PVRL2和PVR为中心的免疫调节机制,并阐明其在各类癌症中的意义。
In recent years, immunotherapy has emerged as a crucial component of cancer treatment.
However, its efficacy remains limited across various cancer types, highlighting unmet needs. Poliovirus receptor-related 2 (PVRL2) and Poliovirus receptor (PVR) are members of the Nectin and Nectin-like Molecules family, known for their role as cell-cell adhesion molecules.
With the development of immunotherapy, their involvement in tumor immune mechanisms as immune checkpoint factors has garnered significant attention. PVRL2 and PVR are predominantly expressed on tumor cells and antigen-presenting cells, binding to PVRIG and TIGIT, respectively, which are primarily found on T and NK cells, thereby suppressing antitumor immunity.
Notably, gynecological cancers such as ovarian and endometrial cancers exhibit high expression levels of PVRL2 and PVR, with similar trends observed in various other solid and hematologic tumors. Targeting these immune checkpoint pathways offers a promising therapeutic avenue, potentially in combination with existing treatments.
However, the immunomodulatory mechanism involving these bindings, known as the DNAM-1 axis, is complex, underscoring the importance of understanding it for developing novel therapies. This article comprehensively reviews the immunomodulatory mechanisms centered on PVRL2 and PVR, elucidating their implications for various cancer types.
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