Human virome profiling identified CMV as the major viral driver of a high accumulation of senescent CD8+ T cells in patients with advanced NSCLC.
Sci Adv
; 9(45): eadh0708, 2023 11 10.
Article
em En
| MEDLINE
| ID: mdl-37939189
ABSTRACT
Circulating senescent CD8+ T (T8sen) cells are characterized by a lack of proliferative capacities but retain cytotoxic activity and have been associated to resistance to immunotherapy in patients with advanced non-small cell lung cancer (aNSCLC). We aimed to better characterize T8sen and to determine which factors were associated with their accumulation in patients with aNSCLC. Circulating T8sen cells were characterized by a higher expression of SA-ßgal and the transcription factor T-bet, confirming their senescent status. Using whole virome profiling, cytomegalovirus (CMV) was the only virus associated with T8sen. CMV was necessary but not sufficient to explain high accumulation of T8sen (T8senhigh status). In CMV+ patients, the proportion of T8sen cells increased with cancer progression. Last, CMV-induced T8senhigh phenotype but not CMV seropositivity itself was associated with worse progression-free and overall survival in patients treated with anti-PD-(L)1 therapy but not with chemotherapy. Overall, CMV is the unique viral driver of T8sen-driven resistance to anti-PD-(L)1 antibodies in patients with aNSCLC.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Pulmonar de Células não Pequenas
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Infecções por Citomegalovirus
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Neoplasias Pulmonares
Limite:
Humans
Idioma:
En
Revista:
Sci Adv
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
França