Proteogenomic characterization of pulmonary large-cell neuroendocrine carcinoma identifies molecular features and therapeutic strategy.
Proteogenomic profiling of tumors and paired normal adjacent tissues from 107 patients with pulmonary large-cell neuroendocrine carcinoma (81 pure, 26 combined) identified three subtypes with distinct prognosis, microenvironment dysregulation, genetic alterations and therapeutic targets. APOBEC mutational signatures correlated with tumor initiation and immune suppression, and KEAP1 mutations with metabolic reprogramming in combined LCNEC. IL-33 emerged as a therapeutic biomarker linked to T cell infiltration, and a PEGylated recombinant IL-33 showed prolonged circulation in cynomolgus monkeys and superior immune agonist activity in mouse models.
It defines LCNEC molecular subtypes and nominates a PEGylated IL-33 immunoagonist strategy for a lung cancer with few options.
Source: 顶刊论文（社媒热度）