Jafri Zuhayr, Zhang Jingwen, O'Meara Connor H, Joshua Anthony M, Parish Christopher R, Khachigian Levon M
Vascular Biology and Translational Research, Department of Pathology, School of Biomedical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia.
Vascular Biology and Translational Research, Department of Pathology, School of Biomedical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia; Division of Head & Neck Oncology and Microvascular Reconstruction, Department of Otolaryngology, Head & Neck Surgery, University of Virginia Health Services, Charlottesville, VA 22903, USA; Department of Otolaryngology, Head & Neck Surgery, Australian National University, Acton, ACT 0200, Australia.
Vascul Pharmacol. 2025 Mar;158:107461. doi: 10.1016/j.vph.2024.107461. Epub 2024 Dec 27.
Immune checkpoint therapy targeting the PD-1/PD-L1 axis has revolutionised the treatment of solid tumors. However, T cell exhaustion underpins resistance to current anti-PD-1 therapies, resulting in lower response rates in cancer patients. CD28 is a T cell costimulatory receptor that can influence the PD-1 signalling pathway (and vice versa). CD28 signalling has the potential to counter T cell exhaustion by serving as a potential complementary response to traditional anti-PD-1 therapies. Here we discuss the interplay between PD-1 and CD28 in T cell immunotherapy and additionally how CD28 transcriptionally modulates T cell exhaustion. We also consider clinical attempts at targeting CD28; the challenges faced by past attempts and recent promising developments.
靶向PD-1/PD-L1轴的免疫检查点疗法彻底改变了实体瘤的治疗方式。然而，T细胞耗竭是当前抗PD-1疗法耐药的基础，导致癌症患者的缓解率较低。CD28是一种T细胞共刺激受体，可影响PD-1信号通路（反之亦然）。CD28信号传导有可能通过作为对传统抗PD-1疗法的潜在补充反应来对抗T细胞耗竭。在此，我们讨论T细胞免疫疗法中PD-1与CD28之间的相互作用，此外还讨论CD28如何在转录水平上调节T细胞耗竭。我们还考虑了针对CD28的临床尝试；过去尝试所面临的挑战以及近期有前景的进展。
