Blood-based molecular and cellular biomarkers of early response to neoadjuvant PD-1 blockade in patients with non-small cell lung cancer

Autor: Xi Zhang, Rui Chen, Zirong Huo, Wenqing Li, Mengju Jiang, Guodong Su, Yuru Liu, Yu Cai, Wuhao Huang, Yuyan Xiong, Shengguang Wang
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Cancer Cell International, Vol 24, Iss 1, Pp 1-16 (2024)
Druh dokumentu: article
ISSN: 1475-2867
DOI: 10.1186/s12935-024-03412-3
Popis: Abstract Background Despite the improved survival observed in PD-1/PD-L1 blockade therapy, a substantial proportion of cancer patients, including those with non-small cell lung cancer (NSCLC), still lack a response. Methods Transcriptomic profiling was conducted on a discovery cohort comprising 100 whole blood samples, as collected multiple times from 48 healthy controls (including 43 published data) and 31 NSCLC patients that under treatment with a combination of anti-PD-1 Tislelizumab and chemotherapy. Differentially expressed genes (DEGs), simulated immune cell subsets, and germline DNA mutational markers were identified from patients achieved a pathological complete response during the early treatment cycles. The predictive values of mutational markers were further validated in an independent immunotherapy cohort of 1661 subjects, and then confirmed in genetically matched lung cancer cell lines by a co-culturing model. Results The gene expression of hundreds of DEGs (FDR p 2) distinguished responders from healthy controls, indicating the potential to stratify patients utilizing early on-treatment features from blood. PD-1-mediated cell abundance changes in memory CD4 + and regulatory T cell subset were more significant or exclusively observed in responders. A panel of top-ranked genetic alterations showed significant associations with improved survival (p
Databáze: Directory of Open Access Journals
Nepřihlášeným uživatelům se plný text nezobrazuje