衰老
癌症研究
表型
生物
转录因子
胶质母细胞瘤
替莫唑胺
癌症
肿瘤进展
免疫组织化学
医学
基因
免疫学
遗传学
作者
Rana Salam,Alexa Saliou,Franck Bielle,Mathilde Bertrand,Christophe Antoniewski,Catherine Carpentier,Agustí Alentorn,Césari Laurent,Marc Sanson,Emmanuelle Huillard,Léa Bellenger,Justine Guégan,Isabelle Le Roux
标识
DOI:10.1038/s41467-023-36124-9
摘要
Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, yet it remains refractory to systemic therapy. Elimination of senescent cells has emerged as a promising new treatment approach against cancer. Here, we investigated the contribution of senescent cells to GBM progression. Senescent cells are identified in patient and mouse GBMs. Partial removal of p16Ink4a-expressing malignant senescent cells, which make up less than 7 % of the tumor, modifies the tumor ecosystem and improves the survival of GBM-bearing female mice. By combining single cell and bulk RNA sequencing, immunohistochemistry and genetic knockdowns, we identify the NRF2 transcription factor as a determinant of the senescent phenotype. Remarkably, our mouse senescent transcriptional signature and underlying mechanisms of senescence are conserved in patient GBMs, in whom higher senescence scores correlate with shorter survival times. These findings suggest that senolytic drug therapy may be a beneficial adjuvant therapy for patients with GBM.
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