A novel, inflamed small cell lung cancer transcriptional subtype, SCLC-I, defines a subset of patients with distinct immunotherapy vulnerability

摘要: BackgroundSmall cell lung cancer (SCLC) is an aggressive neuroendocrine malignancy with dismal survival outcomes and no established predictive biomarkers. The landmark randomized, phase III IMpower133 trial established the new frontline standard of care for extensive-stage SCLC (ES-SCLC) as etoposide/platinum (EP) plus immune checkpoint blockade (ICB) [anti-PD-L1; atezolizumab (atezo)] based on an overall survival (OS) benefit compared to EP plus placebo. However, this survival benefit is limited in unselected populations, emphasizing the need for predictive biomarkers. Preclinically, there is emerging evidence of transcriptional heterogeneity among SCLC tumors, but the impact on therapeutic benefit remains undefined. Using non-negative matrix factorization (NMF) analysis of gene expression data from 81 SCLC tumors samples, we previously identified four subtypes, including three defined …