ArticleDiscover oncology2026
Association of HLA-I genotypic diversity with tumor mutational burden across cancer types in a large Chinese cohort.
Article in Discover oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Advances in linear epitope-based subunit vaccines powered by artificial intelligence: current status and challenges.Frontiers in immunology · 2026Review
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5 authors.
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Abstract
backgroundHLA-I polymorphism influences tumor antigen presentation and immune response. The interplay between HLA-I genotype, heterozygosity, and TMB across cancer types remains poorly understood.
methodsWe analyzed whole-exome sequencing (WES) data from 810 cancer patients across 21 cancer types, enrolled between January 2021 and July 2024. HLA genotyping was performed using HLAscan, and heterozygosity was assessed. Clustering of HLA genotypes was conducted using HLAClustRView.
resultsHLA class I loci exhibited considerable polymorphism, with the most frequent alleles being A11:01/A24:02, B40:01/B46:01, and C01:02/C07:02. The predominant allele groups were A02, B40, and C03. In the cohort, 79.88% of patients were all-heterozygous. Unsupervised clustering based on HLA allele composition revealed six distinct clusters. TMB analysis identified a significant association between one HLA-B allele group and TMB (P = 0.025). TMB varied across HLA clusters (P = 0.069), with cluster #2 showing the highest and cluster #6 the lowest TMB. Overall, no significant TMB differences were observed between the all-heterozygous and any-homozygous groups. However, in most cancer types, the all-heterozygous group was associated with higher TMB, especially in liver cancer (P = 0.013). In contrast, in gastric cancer, TMB was significantly lower in the all-heterozygous group (P = 0.030), multivariate analysis confirmed that MSI-H, rather than HLA heterozygosity, was the independent factor influencing TMB (P < 0.001). In liver cancer, mutations in MUC16 and EPPK1 were significantly enriched in the all-heterozygous group, whereas mutations in DSPP were significantly enriched in the any-homozygous group.
conclusionThis study elucidates the relationship between HLA-I polymorphism, heterozygosity, and TMB across cancers. Future research integrating HLA genotype and TMB could optimize immunotherapy strategies in diverse populations.
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