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- Title
Assessment of human leukocyte antigen-based neoantigen presentation to determine pan-cancer response to immunotherapy.
- Authors
Han, Jiefei; Dong, Yiting; Zhu, Xiuli; Reuben, Alexandre; Zhang, Jianjun; Xu, Jiachen; Bai, Hua; Duan, Jianchun; Wan, Rui; Zhao, Jie; Bai, Jing; Xia, Xuefeng; Yi, Xin; Cheng, Chao; Wang, Jie; Wang, Zhijie
- Abstract
Despite the central role of human leukocyte antigen class I (HLA-I) in tumor neoantigen presentation, quantitative determination of presentation capacity remains elusive. Based on a pooled pan-cancer genomic dataset of 885 patients treated with immune checkpoint inhibitors (ICIs), we developed a score integrating the binding affinity of neoantigens to HLA-I, as well as HLA-I allele divergence, termed the HLA tumor-Antigen Presentation Score (HAPS). Patients with a high HAPS were more likely to experience survival benefit following ICI treatment. Analysis of the tumor microenvironment indicated that the antigen presentation pathway was enriched in patients with a high HAPS. Finally, we built a neural network incorporating factors associated with neoantigen production, presentation, and recognition, which exhibited potential for differentiating cancer patients likely to benefit from ICIs. Our findings highlight the clinical utility of evaluating HLA-I tumor antigen presentation capacity and describe how ICI response may depend on HLA-mediated immunity. HLA-I plays a key role in triggering an immune response and predicting immune checkpoint efficacy. Here the authors develop a method for quantifying HLA-I neoantigen presentation capacity by integrating HLA-I allele divergence and neoantigens numbers, termed HAPS, to describe how immune checkpoint response may be mediated by HLA.
- Subjects
HISTOCOMPATIBILITY class I antigens; ALLELES; IMMUNE checkpoint inhibitors; IMMUNE checkpoint proteins; ANTIGEN presentation; TUMOR antigens
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-45361-5