Yarchoan Mark, Johnson Burles A, Lutz Eric R, Laheru Daniel A, Jaffee Elizabeth M
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA.
Nat Rev Cancer. 2017 Apr;17(4):209-222. doi: 10.1038/nrc.2016.154. Epub 2017 Feb 24.
The past decade of cancer research has been marked by a growing appreciation of the role of immunity in cancer. Mutations in the tumour genome can cause tumours to express mutant proteins that are tumour specific and not expressed on normal cells (neoantigens). These neoantigens are an attractive immune target because their selective expression on tumours may minimize immune tolerance as well as the risk of autoimmunity. In this Review we discuss the emerging evidence that neoantigens are recognized by the immune system and can be targeted to increase antitumour immunity. We also provide a framework for personalized cancer immunotherapy through the identification and selective targeting of individual tumour neoantigens, and present the potential benefits and obstacles to this approach of targeted immunotherapy.
过去十年的癌症研究显著体现出人们对免疫在癌症中作用的认识不断加深。肿瘤基因组中的突变可导致肿瘤表达肿瘤特异性且在正常细胞上不表达的突变蛋白(新抗原)。这些新抗原是有吸引力的免疫靶点,因为它们在肿瘤上的选择性表达可将免疫耐受以及自身免疫风险降至最低。在本综述中,我们讨论了新证据,即新抗原可被免疫系统识别,且可作为靶点来增强抗肿瘤免疫力。我们还通过识别和选择性靶向个体肿瘤新抗原,为个性化癌症免疫疗法提供了一个框架,并阐述了这种靶向免疫疗法的潜在益处和障碍。