小柯机器人

美国约翰·霍普金斯大学医学院Mary Armanios研究小组发现，T细胞免疫缺陷而非染色体不稳定使短端粒综合征患者容易患鳞癌。2023年4月2日，国际知名学术期刊《癌细胞》在线发表了这一成果。

研究人员表示，短端粒综合征（STS）的患者容易患癌症，这被认为是源于肿瘤细胞的染色体不稳定。

研究人员在过去20年中收集的一个大型队列中测试了这个假设。研究人员发现STS患者只易患头颈部、肛门或皮肤的鳞状细胞癌，这个谱系让人联想到在免疫缺陷患者身上看到的癌症。全基因组测序显示染色体不稳定性没有增加，如易位或染色体三体。

此外，STS相关的癌症获得了端粒维持机制，包括端粒酶逆转录酶（TERT）启动子突变。对STS患者的免疫状态的详细研究显示，在癌症诊断时有一个惊人的T细胞免疫缺陷。在端粒较短的小鼠中也记录了类似的免疫缺陷，它损害了对肿瘤的监控。研究人员认为，STS患者对实体癌的易感性是由于T细胞衰竭而不是肿瘤细胞本身的自主缺陷造成的。

附：英文原文

Title: T cell immune deficiency rather than chromosome instability predisposes patients with short telomere syndromes to squamous cancers

Author: Kristen E. Schratz, Diane A. Flasch, Christine C. Atik, Zoe L. Cosner, Amanda L. Blackford, Wentao Yang, Dustin L. Gable, Paz J. Vellanki, Zhimin Xiang, Valeriya Gaysinskaya, Robert H. Vonderheide, Lisa M. Rooper, Jinghui Zhang, Mary Armanios

Issue&Volume: 2023-04-02

Abstract: Patients with short telomere syndromes (STS) are predisposed to developing cancer, believed to stem from chromosome instability in neoplastic cells. We tested this hypothesis in a large cohort assembled over the last 20 years. We found patients with STS are only predisposed to squamous cell carcinoma of the head and neck, anus, or skin, a spectrum reminiscent of cancers seen in patients with immunodeficiency. Whole-genome sequencing showed no increase in chromosome instability, such as translocations or chromothripsis. Moreover, STS-associated cancers acquired telomere maintenance mechanisms, including telomerase reverse transcriptase (TERT) promoter mutations. A detailed study of the immune status of patients with STS revealed a striking T cell immunodeficiency at the time of cancer diagnosis. A similar immunodeficiency that impaired tumor surveillance was documented in mice with short telomeres. We conclude that STS patients’ predisposition to solid cancers is due to T cell exhaustion rather than autonomous defects in the neoplastic cells themselves.

DOI: 10.1016/j.ccell.2023.03.005

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00078-8

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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