Hitting the complexity of the TIGIT-CD96-CD112R-CD226 axis for next-generation cancer immunotherapy.
Hitting the complexity of the TIGIT-CD96-CD112R-CD226 axis for next-generation cancer immunotherapy.
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DOI：
10.5483/bmbrep.2021.54.1.229
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发表时间：
2021-01
期刊：
影响因子：
3.8
通讯作者：
Park Y
中科院分区：
文献类型：
--
作者：
Jin HS;Park Y
靶向抑制性受体PD-1、PD-L1或CTLA-4的基于抗体的治疗剂已经在几种癌症上显示出显著的临床进展。然而，大多数患者并没有从这些治疗中获益。因此，正在进行许多努力来鉴定新的免疫检查点受体-配体途径，这些途径是癌症免疫疗法的替代靶点。Nectin和Nectin样分子广泛表达于几种类型的肿瘤细胞上，并在T细胞和NK细胞功能中发挥调节作用。淋巴样细胞上的TIGIT、CD 226、CD 96和CD 112 R是一组免疫球蛋白超家族受体，其以不同的亲和力与Nectin和Nectin样分子相互作用。这些受体在将其同源配体结合至免疫细胞后传递激活或抑制信号。它们复杂的相互作用形成的整合信号有助于调节免疫细胞功能。几项临床试验目前正在评估抗TIGIT和抗CD 112 R阻断剂用于治疗实体瘤患者的功效。然而，许多问题仍然需要回答，以充分了解这些受体网络的动态和功能。本文综述了靶向TIGIT、CD 226、CD 96和CD 112 R调节T细胞和NK细胞功能的原理，并讨论了它们在癌症免疫治疗中的潜在应用。
Antibody-based therapeutics targeting the inhibitory receptors PD-1, PD-L1, or CTLA-4 have shown remarkable clinical progress on several cancers. However, most patients do not benefit from these therapies. Thus, many efforts are being made to identify new immune checkpoint receptor-ligand pathways that are alternative targets for cancer immunotherapies. Nectin and nectin-like molecules are widely expressed on several types of tumor cells and play regulatory roles in T- and NK-cell functions. TIGIT, CD226, CD96 and CD112R on lymphoid cells are a group of immunoglobulin superfamily receptors that interact with Nectin and nectin-like molecules with different affinities. These receptors transmit activating or inhibitory signals upon binding their cognate ligands to the immune cells. The integrated signals formed by their complex interactions contribute to regu-lating immune-cell functions. Several clinical trials are currently evaluating the efficacy of anti-TIGIT and anti-CD112R blockades for treating patients with solid tumors. However, many questions still need to be answered in order to fully understand the dynamics and functions of these receptor networks. This review addresses the rationale behind targeting TIGIT, CD226, CD96, and CD112R to regulate T- and NK-cell functions and discusses their potential application in cancer immunotherapy.