Assessment of human leukocyte antigen-based neoantigen presentation to determine pan-cancer response to immunotherapy

Jiefei Han, Yiting Dong, Xiuli Zhu, Alexandre Reuben, Jianjun Zhang, Jiachen Xu, Hua Bai, Jianchun Duan, Rui Wan, Jie Zhao, Jing Bai, Xuefeng Xia, Xin Yi, Chao Cheng (), Jie Wang () and Zhijie Wang ()
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Jiefei Han: Chinese Academy of Medical Sciences and Peking Union Medical College
Yiting Dong: Chinese Academy of Medical Sciences and Peking Union Medical College
Xiuli Zhu: Geneplus-Beijing Institute
Alexandre Reuben: The University of Texas M. D. Anderson Cancer Center
Jianjun Zhang: The University of Texas M. D. Anderson Cancer Center
Jiachen Xu: Chinese Academy of Medical Sciences and Peking Union Medical College
Hua Bai: Chinese Academy of Medical Sciences and Peking Union Medical College
Jianchun Duan: Chinese Academy of Medical Sciences and Peking Union Medical College
Rui Wan: Chinese Academy of Medical Sciences and Peking Union Medical College
Jie Zhao: Chinese Academy of Medical Sciences and Peking Union Medical College
Jing Bai: Geneplus-Beijing Institute
Xuefeng Xia: Geneplus-Beijing Institute
Xin Yi: Geneplus-Beijing Institute
Chao Cheng: Baylor College of Medicine
Jie Wang: Chinese Academy of Medical Sciences and Peking Union Medical College
Zhijie Wang: Chinese Academy of Medical Sciences and Peking Union Medical College

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-45361-5

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