Human virome profiling identified CMV as the major viral driver of a high accumulation of senescent CD8+ T cells in patients with advanced NSCLC
Menée à partir notamment d'échantillons sanguins et de données cliniques portant sur des patients atteints d'un cancer du poumon non à petites cellules de stade avancé, cette étude met en évidence une association entre le cytomégalovirus et l'accumulation de lymphocytes CD8+ sénescents
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-βgal 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. CMV is the main viral driver of T8sen-induced resistance to anti-PD-(L)1 in patients with aNSCLC.
Science Advances , article en libre accès, 2022