B7/CD28 免疫检查点家族的最新进展：新的生物学和临床治疗策略。
Recent advancements in the B7/CD28 immune checkpoint families: new biology and clinical therapeutic strategies.
机构信息
Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, 10461, USA.
Department of Urology, Albert Einstein College of Medicine, New York, NY, 10461, USA.
出版信息
Cell Mol Immunol. 2023 Jul;20(7):694-713. doi: 10.1038/s41423-023-01019-8. Epub 2023 Apr 17.
Abstract
The B7/CD28 families of immune checkpoints play vital roles in negatively or positively regulating immune cells in homeostasis and various diseases. Recent basic and clinical studies have revealed novel biology of the B7/CD28 families and new therapeutics for cancer therapy. In this review, we discuss the newly discovered KIR3DL3/TMIGD2/HHLA2 pathways, PD-1/PD-L1 and B7-H3 as metabolic regulators, the glycobiology of PD-1/PD-L1, B7x (B7-H4) and B7-H3, and the recently characterized PD-L1/B7-1 cis-interaction. We also cover the tumor-intrinsic and -extrinsic resistance mechanisms to current anti-PD-1/PD-L1 and anti-CTLA-4 immunotherapies in clinical settings. Finally, we review new immunotherapies targeting B7-H3, B7x, PD-1/PD-L1, and CTLA-4 in current clinical trials.
摘要
B7/CD28 家族的免疫检查点在维持免疫细胞的稳态和各种疾病中发挥着重要作用，可负向或正向调节免疫细胞。最近的基础和临床研究揭示了 B7/CD28 家族的新生物学和癌症治疗的新疗法。在这篇综述中，我们讨论了新发现的 KIR3DL3/TMIGD2/HHLA2 途径、PD-1/PD-L1 和 B7-H3 作为代谢调节剂、PD-1/PD-L1 的糖生物学、B7x（B7-H4）和 B7-H3 以及最近描述的 PD-L1/B7-1 顺式相互作用。我们还涵盖了目前在临床环境中针对抗 PD-1/PD-L1 和抗 CTLA-4 免疫疗法的肿瘤内在和外在耐药机制。最后，我们综述了目前临床试验中针对 B7-H3、B7x、PD-1/PD-L1 和 CTLA-4 的新型免疫疗法。
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