Substantial progress in understanding T cell signalling, particularly with respect to T cell co-receptors such as the co-stimulatory receptor CD28, has been made in recent years. This knowledge has been instrumental in the development of innovative immunotherapies for patients with cancer, including immune checkpoint blockade antibodies, adoptive cell therapies, tumour-targeted immunostimulatory antibodies, and immunostimulatory small-molecule drugs that regulate T cell activation. Following the failed clinical trial of a CD28 superagonist antibody in 2006, targeted CD28 agonism has re-emerged as a technologically viable and clinically promising strategy for cancer immunotherapy. In this Review, we explore recent insights into the molecular functions and regulation of CD28. We describe how CD28 is central to the success of current cancer immunotherapies and examine how new questions arising from studies of CD28 as a clinical target have enhanced our understanding of its biological role and may guide the development of future therapeutic strategies in oncology.

近年来，在理解 T 细胞信号传导方面取得了重大进展，特别是在 T 细胞辅助受体（如共刺激受体 CD28）方面。这些知识有助于为癌症患者开发创新的免疫疗法，包括免疫检查点阻断抗体、过继细胞疗法、肿瘤靶向免疫刺激抗体和调节 T 细胞活化的免疫刺激小分子药物。在 2006 年 CD28 超级激动剂抗体临床试验失败后，靶向 CD28 激动剂再次成为一种技术上可行且有临床前景的癌症免疫治疗策略。在这篇综述中，我们探讨了对 CD28 分子功能和调控的最新见解。我们描述了 CD28 如何成为当前癌症免疫疗法成功的核心，并研究了 CD28 作为临床靶点的研究如何增强我们对其生物学作用的理解，并可能指导未来肿瘤学治疗策略的开发。