T cell immune deficiency rather than chromosome instability predisposes patients with short telomere syndromes to squamous cancers.
Cancer Cell
; 41(4): 807-817.e6, 2023 04 10.
Article
em En
| MEDLINE
| ID: mdl-37037617
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 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.
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Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Células Escamosas
/
Telomerase
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article