化疗
肺癌
免疫系统
肿瘤科
内科学
PD-L1
免疫疗法
肿瘤微环境
基因签名
医学
癌症研究
免疫学
生物
基因表达
基因
生物化学
作者
Jianchun Duan,Yun Zhang,Ran Chen,Liang Liang,Yi Huang,Shun Lü,Jun Zhao,Chunhong Hu,Yehuan Sun,Kunyu Yang,Mingwei Chen,Yan Yu,Jianming Ying,Ruiqi Huang,Xiaopeng Ma,Shiangjiin Leaw,Fan Bai,Zhirong Shen,Shangli Cai,Daming Gao,Jie Wang,Zhijie Wang
标识
DOI:10.1016/j.xcrm.2023.101302
摘要
The RATIONALE-307 study (ClinicalTrials.gov: NCT03594747) demonstrates prolonged progression-free survival (PFS) with first-line tislelizumab plus chemotherapy versus chemotherapy in advanced lung squamous cell carcinoma (LUSC; N = 360). Here we describe an immune-related gene expression signature (GES), composed of genes involved in both innate and adaptive immunity, that appears to differentiate tislelizumab plus chemotherapy PFS benefit versus chemotherapy. In contrast, a tislelizumab plus chemotherapy PFS benefit is observed regardless of programmed death ligand 1 (PD-L1) expression or tumor mutational burden (TMB). Genetic analysis reveals that NRF2 pathway activation is enriched in PD-L1positive and TMBhigh patients. NRF2 pathway activation is negatively associated with PFS, which affects efficacy outcomes associated with PD-L1 and TMB status, impairing their predictive potential. Mechanistic studies demonstrate that NRF2 directly mediates PD-L1 constitutive expression independent of adaptive PD-L1 regulation in LUSC. In summary, the GES is an immune signature that might identify LUSC patients likely to benefit from first-line tislelizumab plus chemotherapy.
科研通智能强力驱动
Strongly Powered by AbleSci AI