The Mary and Garry Weston Molecular Immunology Laboratory, Thrombosis Research Institute, London- SW3 6LR, United Kingdom.
Curr Med Chem. 2021;28(28):5659-5673. doi: 10.2174/0929867328666201229123151.
OX40 (CD134) and its binding partner, OX40L (CD252), are expressed on activated CD4, CD8 T-cells, and several other lymphoid and non-lymphoid cells. OX40L belongs to a TNF family member, a 34 kDa type II transmembrane protein. The crystallized complex of human OX40 and OX40L is a trimeric contableuration of one OX40L (trimer) and three OX40 monomers. OX40 and OX40L regulate cytokine production from T-cells, antigen-presenting cells, and natural killer (NK) cells, and modulate cytokine receptor signaling.
In this review, an updated overview of the structural features of OX40/OX40L and their interactions with cancer are provided.
Recent studies have shown that stimulation of OX40 is useful for therapeutic immunization strategies for cancer. OX40 serves as a secondary costimulatory immune checkpoint molecule; the binding of OX40 to its ligand enhances the augmentation, survival, memory formation, effector function, and recall responses of both CD4+ and CD8+ T-cells.
This review highlights that OX40-OX40L interactions play crucial roles in both CD4+ and CD8+ T-cells. Signals through OX40 can abolish the suppressive activity of Tregs, prevent the induction of Tregs from effector T-cells, reduce Foxp3 expression, and induce the proliferation of memory and effector T lymphocytes. Additionally, when transferred into tumor-bearing recipients, they generate proliferation capability and successfully eliminate the established tumor.
OX40（CD134）及其配体 OX40L（CD252）表达于活化的 CD4、CD8 T 细胞和其他一些淋巴和非淋巴样细胞上。OX40L 属于 TNF 家族成员，是一种 34kDa 的 II 型跨膜蛋白。人 OX40 和 OX40L 的结晶复合物是一个三聚体，由一个 OX40L（三聚体）和三个 OX40 单体组成。OX40 和 OX40L 调节 T 细胞、抗原呈递细胞和自然杀伤（NK）细胞的细胞因子产生，并调节细胞因子受体信号。
在这篇综述中，提供了 OX40/OX40L 的结构特征及其与癌症相互作用的最新概述。
最近的研究表明，刺激 OX40 可用于癌症的治疗性免疫接种策略。OX40 作为一种辅助性免疫检查点分子；OX40 与其配体的结合增强了 CD4+和 CD8+T 细胞的扩增、存活、记忆形成、效应功能和回忆反应。
本综述强调了 OX40-OX40L 相互作用在 CD4+和 CD8+T 细胞中都起着至关重要的作用。通过 OX40 传递的信号可以消除 Treg 的抑制活性，防止效应 T 细胞诱导 Treg 的产生，减少 Foxp3 的表达，并诱导记忆和效应 T 淋巴细胞的增殖。此外，当转移到荷瘤受体中时，它们会产生增殖能力，并成功消除已建立的肿瘤。
