MHC-Hammer decodes HLA disruption in tumors

Abstract

Tumors utilize various mechanisms of HLA disruption in order to evade immune surveillance. Previous computational tools have interrogated specific aspects of this process, yet a holistic picture of HLA loss of heterozygosity (LOH), transcriptomic suppression, and alternative splicing has remained challenging. In a recent Nature Genetics study, Puttick and colleagues introduced MHC Hammer, a robust computational toolkit designed to dissect the complexities of HLA disruptions that mediate immune evasion in cancer. By analyzing comprehensive genomic and transcriptomic data across several large cancer cohorts, the study highlights the prevalence of HLA disruptions–particularly alternative splicing events–across various tumor types and identifies HLA LOH as an important immune evasion mechanism during metastasis in lung adenocarcinoma.