CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Emergence of the CD226 Axis in Cancer Immunotherapy.
Emergence of the CD226 Axis in Cancer Immunotherapy.
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近年来,一组与nectin/nectin样(necl)家族成员相互作用的免疫受体作为癌症潜在干预靶点引起了广泛关注。CD226、TIGIT和CD96是该轴的核心,代表配体(CD155)竞争性共刺激/抑制性受体,类似于CTLA-4/B7/CD28三联体。PVRIG(CD112R)和CD112的发现引入了复杂性,并开辟了额外的治疗干预节点。凭借TIGIT拮抗剂的临床进展以及基于CD96和PVRIG的新型方法的出现,我们对癌症免疫治疗中“CD226轴”的整体理解正开始成形。
然而,关于每个受体-配体对的独特特征及其机制性相互作用,仍存在若干问题。本综述在癌症背景下概述了CD226轴,重点关注免疫治疗策略(TIGIT、CD96和PVRIG)的现状及其潜在生物学机制(即顺式/反式相互作用)。
我们还整合了关于所涉及免疫细胞群的新兴知识、Fcγ受体生物学在治疗活性中的关键考量,以及快速演变的临床格局概览。
In recent years, a set of immune receptors that interact with members of the nectin/nectin-like (necl) family has garnered significant attention as possible points of manipulation in cancer. Central to this axis, CD226, TIGIT, and CD96 represent ligand (CD155)-competitive co-stimulatory/inhibitory receptors, analogous to the CTLA-4/B7/CD28 tripartite.
The identification of PVRIG (CD112R) and CD112 has introduced complexity and enabled additional nodes of therapeutic intervention. By virtue of the clinical progression of TIGIT antagonists and emergence of novel CD96- and PVRIG-based approaches, our overall understanding of the 'CD226 axis' in cancer immunotherapy is starting to take shape.
However, several questions remain regarding the unique characteristics of, and mechanistic interplay between, each receptor-ligand pair. This review provides an overview of the CD226 axis in the context of cancer, with a focus on the status of immunotherapeutic strategies (TIGIT, CD96, and PVRIG) and their underlying biology (i. e. , cis / trans interactions).
We also integrate our emerging knowledge of the immune populations involved, key considerations for Fc gamma (γ) receptor biology in therapeutic activity, and a snapshot of the rapidly evolving clinical landscape.
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