Background: 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.

Methods: In this review, an updated overview of the structural features of OX40/OX40L and their interactions with cancer are provided.

Results: 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.

Conclusion: 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.

背景：OX40 (CD134) 及其结合伴侣 OX40L (CD252) 在活化的 CD4、CD8 T 细胞以及其他几种淋巴和非淋巴细胞上表达。OX40L 属于 TNF 家族成员，一种 34 kDa 的 II 型跨膜蛋白。人 OX40 和 OX40L 的结晶复合物是一个 OX40L（三聚体）和三个 OX40 单体的三聚体结构。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。

方法：在本综述中，提供了 OX40/OX40L 结构特征及其与癌症相互作用的最新概述。

结果：最近的研究表明，OX40 的刺激对于癌症的治疗性免疫策略是有用的。OX40 作为次级共刺激免疫检查点分子；OX40 与其配体的结合增强了 CD4+ 和 CD8+ T 细胞的增强、存活、记忆形成、效应功能和回忆反应。

结论：本综述强调 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的信号可以消除Tregs的抑制活性，阻止效应T细胞对Tregs的诱导，降低Foxp3的表达，并诱导记忆和效应T淋巴细胞的增殖。此外，当转移到荷瘤受体时，它们产生增殖能力并成功消除已建立的肿瘤。