Assessment of human leukocyte antigen-based neoantigen presentation to determine pan-cancer response to immunotherapy
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 develo...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-45361-5 |
| _version_ | 1797274129585405952 |
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| author | 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 Zhijie Wang |
| author_facet | 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 Zhijie Wang |
| author_sort | Jiefei Han |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T14:53:57Z |
| format | Article |
| id | doaj.art-d81e01705721423fa5028798af08893d |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:53:57Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-d81e01705721423fa5028798af08893d2024-03-05T19:33:04ZengNature PortfolioNature Communications2041-17232024-02-0115111510.1038/s41467-024-45361-5Assessment of human leukocyte antigen-based neoantigen presentation to determine pan-cancer response to immunotherapyJiefei Han0Yiting Dong1Xiuli Zhu2Alexandre Reuben3Jianjun Zhang4Jiachen Xu5Hua Bai6Jianchun Duan7Rui Wan8Jie Zhao9Jing Bai10Xuefeng Xia11Xin Yi12Chao Cheng13Jie Wang14Zhijie Wang15State Key Laboratory of Molecular Oncology, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Molecular Oncology, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeGeneplus-Beijing InstituteDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer CenterDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer CenterState Key Laboratory of Molecular Oncology, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Molecular Oncology, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Molecular Oncology, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Molecular Oncology, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Molecular Oncology, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeGeneplus-Beijing InstituteGeneplus-Beijing InstituteGeneplus-Beijing InstituteDepartment of Medicine, Dan L Duncan Comprehensive Cancer Center, Institute for Clinical and Translational Research, Baylor College of MedicineState Key Laboratory of Molecular Oncology, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Molecular Oncology, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract 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.https://doi.org/10.1038/s41467-024-45361-5 |
| spellingShingle | 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 Zhijie Wang Assessment of human leukocyte antigen-based neoantigen presentation to determine pan-cancer response to immunotherapy Nature Communications |
| title | Assessment of human leukocyte antigen-based neoantigen presentation to determine pan-cancer response to immunotherapy |
| title_full | Assessment of human leukocyte antigen-based neoantigen presentation to determine pan-cancer response to immunotherapy |
| title_fullStr | Assessment of human leukocyte antigen-based neoantigen presentation to determine pan-cancer response to immunotherapy |
| title_full_unstemmed | Assessment of human leukocyte antigen-based neoantigen presentation to determine pan-cancer response to immunotherapy |
| title_short | Assessment of human leukocyte antigen-based neoantigen presentation to determine pan-cancer response to immunotherapy |
| title_sort | assessment of human leukocyte antigen based neoantigen presentation to determine pan cancer response to immunotherapy |
| url | https://doi.org/10.1038/s41467-024-45361-5 |
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