Targeting B7-H3 enhances the efficacy of neoantigen-based cancer vaccine in combination with radiotherapy
Abstract The clinical response to immune checkpoint blockade (ICB) is limited in the majority of patients with colorectal cancer. These immune checkpoint proteins may not only inhibit T-cell-mediated antitumor immunity but also attenuate antigen presentation, including mutation-associated neoantigen...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-04-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-025-01132-x |
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| author | Tao-Wei Ke Chia-Yi Chen William Tzu-Liang Chen Yuan-Yao Tsai Shu-Fen Chiang Chi-Hsien Huang Yu-Sen Lin Te-Hong Chen Tsung-Wei Chen Ji-An Liang K. S. Clifford Chao Kevin Chih-Yang Huang |
| author_facet | Tao-Wei Ke Chia-Yi Chen William Tzu-Liang Chen Yuan-Yao Tsai Shu-Fen Chiang Chi-Hsien Huang Yu-Sen Lin Te-Hong Chen Tsung-Wei Chen Ji-An Liang K. S. Clifford Chao Kevin Chih-Yang Huang |
| author_sort | Tao-Wei Ke |
| collection | DOAJ |
| description | Abstract The clinical response to immune checkpoint blockade (ICB) is limited in the majority of patients with colorectal cancer. These immune checkpoint proteins may not only inhibit T-cell-mediated antitumor immunity but also attenuate antigen presentation, including mutation-associated neoantigens. Here, we found that tumor B7-H3 levels may limit the therapeutic response to chemoradiotherapy in patients with locally-advanced rectal cancer. Knockdown of tumor B7-H3 significantly increased antigen presentation to increase T cell infiltration and killing ability, including neoantigen-specific T-cell response. Blockade of B7-H3 significantly augmented neoantigen-specific T cells response and remarkably enhanced the therapeutic efficacy of neoantigen-based cancer vaccines combined with radiotherapy, decreasing the risk of distant tumors in vivo. Taken together, these results demonstrated that targeting B7-H3 significantly enhanced the therapeutic efficacy of neoantigen cancer vaccines as well as radiotherapy by increasing the extent of neoantigen-specific T cells, even for PD-1/PD-L1 blockade-resistant colorectal cancers. |
| format | Article |
| id | doaj-art-fe383b028ea34ab38a8fdee69b29b64c |
| institution | OA Journals |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-fe383b028ea34ab38a8fdee69b29b64c2025-08-20T02:30:19ZengNature Portfolionpj Vaccines2059-01052025-04-0110111310.1038/s41541-025-01132-xTargeting B7-H3 enhances the efficacy of neoantigen-based cancer vaccine in combination with radiotherapyTao-Wei Ke0Chia-Yi Chen1William Tzu-Liang Chen2Yuan-Yao Tsai3Shu-Fen Chiang4Chi-Hsien Huang5Yu-Sen Lin6Te-Hong Chen7Tsung-Wei Chen8Ji-An Liang9K. S. Clifford Chao10Kevin Chih-Yang Huang11Department of Colorectal Surgery, China Medical University Hospital, China Medical UniversityProton Therapy Center, China Medical University Hospital, China Medical UniversityDepartment of Colorectal Surgery, China Medical University Hospital, China Medical UniversityDepartment of Colorectal Surgery, China Medical University Hospital, China Medical UniversityLab of Precision Medicine, Feng-Yuan Hospital, Ministry of Health and WelfareGraduate Institute of Biomedical Science, China Medical UniversityDepartment of Chest Surgery, China Medical University HospitalDepartment of Surgery, China Medical University HospitalDepartment of Pathology, Asia University Hospital, Asia UniversityDepartment of Radiation Oncology, China Medical University Hospital, China Medical UniversityProton Therapy Center, China Medical University Hospital, China Medical UniversityDepartment of Biomedical Imaging and Radiological Science, China Medical UniversityAbstract The clinical response to immune checkpoint blockade (ICB) is limited in the majority of patients with colorectal cancer. These immune checkpoint proteins may not only inhibit T-cell-mediated antitumor immunity but also attenuate antigen presentation, including mutation-associated neoantigens. Here, we found that tumor B7-H3 levels may limit the therapeutic response to chemoradiotherapy in patients with locally-advanced rectal cancer. Knockdown of tumor B7-H3 significantly increased antigen presentation to increase T cell infiltration and killing ability, including neoantigen-specific T-cell response. Blockade of B7-H3 significantly augmented neoantigen-specific T cells response and remarkably enhanced the therapeutic efficacy of neoantigen-based cancer vaccines combined with radiotherapy, decreasing the risk of distant tumors in vivo. Taken together, these results demonstrated that targeting B7-H3 significantly enhanced the therapeutic efficacy of neoantigen cancer vaccines as well as radiotherapy by increasing the extent of neoantigen-specific T cells, even for PD-1/PD-L1 blockade-resistant colorectal cancers.https://doi.org/10.1038/s41541-025-01132-x |
| spellingShingle | Tao-Wei Ke Chia-Yi Chen William Tzu-Liang Chen Yuan-Yao Tsai Shu-Fen Chiang Chi-Hsien Huang Yu-Sen Lin Te-Hong Chen Tsung-Wei Chen Ji-An Liang K. S. Clifford Chao Kevin Chih-Yang Huang Targeting B7-H3 enhances the efficacy of neoantigen-based cancer vaccine in combination with radiotherapy npj Vaccines |
| title | Targeting B7-H3 enhances the efficacy of neoantigen-based cancer vaccine in combination with radiotherapy |
| title_full | Targeting B7-H3 enhances the efficacy of neoantigen-based cancer vaccine in combination with radiotherapy |
| title_fullStr | Targeting B7-H3 enhances the efficacy of neoantigen-based cancer vaccine in combination with radiotherapy |
| title_full_unstemmed | Targeting B7-H3 enhances the efficacy of neoantigen-based cancer vaccine in combination with radiotherapy |
| title_short | Targeting B7-H3 enhances the efficacy of neoantigen-based cancer vaccine in combination with radiotherapy |
| title_sort | targeting b7 h3 enhances the efficacy of neoantigen based cancer vaccine in combination with radiotherapy |
| url | https://doi.org/10.1038/s41541-025-01132-x |
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