biostudies-literatureGarcia-Marquez MADeutsche Forschungsgemeinschafte007268https://www.ebi.ac.uk/biostudies/studies/S-EPMC11029431biostudies-literatureUnknown12(4)<h4>Background</h4>The individual HLA-I genotype is associated with cancer, autoimmune diseases and infections. This study elucidates the role of germline homozygosity or allelic imbalance of HLA-I loci in esophago-gastric adenocarcinoma (EGA) and determines the resulting repertoires of potentially immunogenic peptides.<h4>Methods</h4>HLA genotypes and sequences of either (1) 10 relevant tumor-associated antigens (TAAs) or (2) patient-specific mutation-associated neoantigens (MANAs) were used to predict good-affinity binders using an in silico approach for MHC-binding (www.iedb.org). Imbalanced or lost expression of HLA-I-A/B/C alleles was analyzed by transcriptome sequencing. FluoroSpot assays and TCR sequencing were used to determine peptide-specific T-cell responses.<h4>Results</h4>We sJournal for immunotherapy of cancerGermline homozygosity and allelic imbalance of HLA-I are common in esophagogastric adenocarcinoma and impair the repertoire of immunogenic peptides.PMC11029431No. 325827080 and No. 418074181George JPeifer MMuller PBruns CGathof BBauer ENikolic MYazbeck AMHillmer AMvon Bergwelt-Baildon MSchloßer HAGarcia-Marquez MAKeller DWennhold KZander TSchroder WThelen MThomas RQuaas ALehmann JMaas LfalseGermline homozygosity and allelic imbalance of HLA-I are common in esophagogastric adenocarcinoma and impair the repertoire of immunogenic peptides.<h4>Background</h4>The individual HLA-I genotype is associated with cancer, autoimmune diseases and infections. This study elucidates the role of germline homozygosity or allelic imbalance of HLA-I loci in esophago-gastric adenocarcinoma (EGA) and determines the resulting repertoires of potentially immunogenic peptides.<h4>Methods</h4>HLA genotypes and sequences of either (1) 10 relevant tumor-associated antigens (TAAs) or (2) patient-specific mutation-associated neoantigens (MANAs) were used to predict good-affinity binders using an in silico approach for MHC-binding (www.iedb.org). Imbalanced or lost expression of HLA-I-A/B/C alleles was analyzed by transcriptome sequencing. FluoroSpot assays and TCR sequencing were used to determine peptide-specific T-cell responses.<h4>Results</h4>We s2024-01-01T00:00:00Z2024 Apr2026-06-15T06:15:49.253Z2026-06-15T03:08:39.132ZS-EPMC110294313863170710.1136/jitc-2023-007268