Division of Molecular Oncology and Immunology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; email:
Oncode Institute, 3521AL Utrecht, The Netherlands.
Annu Rev Immunol. 2019 Apr 26;37:173-200. doi: 10.1146/annurev-immunol-042617-053402. Epub 2018 Dec 14.
Malignant transformation of cells depends on accumulation of DNA damage. Over the past years we have learned that the T cell-based immune system frequently responds to the neoantigens that arise as a consequence of this DNA damage. Furthermore, recognition of neoantigens appears an important driver of the clinical activity of both T cell checkpoint blockade and adoptive T cell therapy as cancer immunotherapies. Here we review the evidence for the relevance of cancer neoantigens in tumor control and the biological properties of these antigens. We discuss recent technological advances utilized to identify neoantigens, and the T cells that recognize them, in individual patients. Finally, we discuss strategies that can be employed to exploit cancer neoantigens in clinical interventions.
细胞的恶性转化取决于 DNA 损伤的积累。在过去的几年中,我们了解到基于 T 细胞的免疫系统经常对作为这种 DNA 损伤后果产生的新抗原作出反应。此外,新抗原的识别似乎是 T 细胞检查点阻断和过继性 T 细胞治疗作为癌症免疫疗法的临床活性的重要驱动因素。在这里,我们回顾了癌症新抗原在肿瘤控制中的相关性以及这些抗原的生物学特性的证据。我们讨论了用于在个体患者中鉴定新抗原和识别它们的 T 细胞的最新技术进展。最后,我们讨论了可以用于在临床干预中利用癌症新抗原的策略。