biostudies-literatureRicciuti BAssociazione Italiana per la Ricerca sul CancroDana-Farber Cancer InstituteMinistero dell’Istruzione, dell’Università e della RicercaNCI NIH HHSEuropean Commission1132-1141https://www.ebi.ac.uk/biostudies/studies/S-EPMC12740342biostudies-literatureUnknown36(10)<h4>Background</h4>Despite significant improvements in overall survival with programmed cell death protein (ligand) 1 [PD-(L)1] inhibition, most patients with metastatic non-small-cell lung cancer (NSCLC) do not respond to immune checkpoint inhibition (ICI). Growing evidence suggests the importance of genomic alterations in modulating anticancer immune response and predicting ICI efficacy. However, the genomic correlates of response to ICI in NSCLC are largely unknown.<h4>Design</h4>Patients with advanced NSCLC treated with ICI and comprehensive genomic profiling from multiple independent cohorts were included. Beta-binomial modelling of sequencing read counts was used to infer mutation clonality. NSCLC samples from Cancer Genome Atlas Program (TCGA) and NSCLC cell lines from Cancer Cell LAnnals of oncology : official journal of the European Society for Medical OncologyDNA methyltransferase 3A (DNMT3A) mutations and PD-(L)1 blockade efficacy in non-small-cell lung cancer.PMC12740342K99 CA297010MFAG 2019CUP H83C2200055000622940PE_00000019Paoloni FZrafi WCappuzzo FAlessi JVMaugeri-Sacca MSholl LMElkrief APecci FCaravagna GSchoenfeld AWang XBesse BScalera SSanto VDi Federico ATagliamento MLamberti GFerrara RAwad MMMiller PGRicciuti BAldea MMicol JBNishino MGariazzo ECalonaci NGarbo EfalseDNA methyltransferase 3A (DNMT3A) mutations and PD-(L)1 blockade efficacy in non-small-cell lung cancer.<h4>Background</h4>Despite significant improvements in overall survival with programmed cell death protein (ligand) 1 [PD-(L)1] inhibition, most patients with metastatic non-small-cell lung cancer (NSCLC) do not respond to immune checkpoint inhibition (ICI). Growing evidence suggests the importance of genomic alterations in modulating anticancer immune response and predicting ICI efficacy. However, the genomic correlates of response to ICI in NSCLC are largely unknown.<h4>Design</h4>Patients with advanced NSCLC treated with ICI and comprehensive genomic profiling from multiple independent cohorts were included. Beta-binomial modelling of sequencing read counts was used to infer mutation clonality. NSCLC samples from Cancer Genome Atlas Program (TCGA) and NSCLC cell lines from Cancer Cell L2025-01-01T00:00:00Z2025 Oct2026-06-06T05:55:00.565Z2026-05-27T03:11:40.261ZS-EPMC127403424054186410.1016/j.annonc.2025.06.003