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

Autor:	Schratz KE; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Telomere Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Flasch DA; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Atik CC; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Cosner ZL; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Blackford AL; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Yang W; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Gable DL; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Vellanki PJ; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Xiang Z; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Gaysinskaya V; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Vonderheide RH; Abramson Cancer Center, Perlman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA., Rooper LM; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Zhang J; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Armanios M; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Telomere Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Electronic address: marmani1@jhmi.edu.
Jazyk:	angličtina
Zdroj:	Cancer cell [Cancer Cell] 2023 Apr 10; Vol. 41 (4), pp. 807-817.e6. Date of Electronic Publication: 2023 Apr 02.
DOI:	10.1016/j.ccell.2023.03.005
Abstrakt:	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 that the only solid cancers to which patients with STS are predisposed are squamous cell carcinomas 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. Competing Interests: Declaration of interests R.H.V. is an inventor on licensed patents related to cancer cellular immunotherapy and cancer vaccines, receives royalties from Boston Children’s Hospital for a licensed research-only monoclonal antibody, and has received consulting fees from Bristol Myers Squibb. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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