T细胞免疫缺陷使得染色体不稳定并不易于引起短端粒综合症患者罹患鳞状细胞癌。
T cell immune deficiency rather than chromosome instability predisposes patients with short telomere syndromes to squamous cancers.
发表日期：2023 Apr 10
作者：
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
来源：
CANCER CELL
摘要：
患有短端粒综合征（STS）的患者易患癌症，这被认为是肿瘤细胞染色体不稳定造成的。我们对过去20年中收集的大量队列进行了此假说的测试。我们发现STS患者只易患头颈部、肛门或皮肤鳞状细胞癌，与免疫缺陷患者中发现的癌症谱相似。全基因组测序显示没有染色体不稳定性的增加，如易位或染色体吞噬症。此外，STS相关癌症获得了端粒维护机制，包括端粒酶逆转录酶（TERT）启动子突变。对STS患者免疫状态进行的详细研究显示，他们在癌症诊断时具有明显的T细胞免疫缺陷。具有短端粒的小鼠中也记录到了类似的影响肿瘤监测的免疫缺陷。我们得出结论，STS患者易患实体癌症是由于T细胞耗竭而非肿瘤细胞自身的自治缺陷。Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
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.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.