Mathematical mechanistic model representing the cancer immunity cycle under radiation effects
Abstract Combining radiotherapy with immune checkpoint inhibitors is a promising approach to improve the effectiveness of cancer treatment. However, the success rates of these clinical studies are limited. It is essential to determine the optimal irradiation scheme that maximizes the therapeutic eff...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-06-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-04715-9 |
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| author | Taisuke Takayanagi Koichi Miyazaki Kana Yamasaki Takahiro Yamada Futaro Ebina Takahiro Kanehira Yasuhito Onodera Keiji Kobashi Hiroshi Taguchi Koichi Yasuda Norio Katoh Takayuki Hashimoto Hidefumi Aoyama Hiroki Shirato Kenji Chamoto |
| author_facet | Taisuke Takayanagi Koichi Miyazaki Kana Yamasaki Takahiro Yamada Futaro Ebina Takahiro Kanehira Yasuhito Onodera Keiji Kobashi Hiroshi Taguchi Koichi Yasuda Norio Katoh Takayuki Hashimoto Hidefumi Aoyama Hiroki Shirato Kenji Chamoto |
| author_sort | Taisuke Takayanagi |
| collection | DOAJ |
| description | Abstract Combining radiotherapy with immune checkpoint inhibitors is a promising approach to improve the effectiveness of cancer treatment. However, the success rates of these clinical studies are limited. It is essential to determine the optimal irradiation scheme that maximizes the therapeutic effect by taking into account the balance between the positive and negative effects of radiation on immunity. In this context, we developed a mathematical mechanistic model that simulates (1) the balance between effector and exhausted cytotoxic T-lymphocytes (CTLs), (2) the number of neoantigens released by high-dose irradiation, and (3) the impact of radiation on draining lymph nodes (DLNs) for systemic anti-tumor immunity, and tested whether this mathematic model fits in several animal experiments. Our mechanistic model reproduced the anti-tumor effects of several cancer treatment models for combination therapies with radiation, immune checkpoint inhibitors, and/or a metabolic modulator. Furthermore, this mechanistic model simulated that tumor suppression in distant metastatic foci, known as the abscopal effect, was dysregulated by hypofractionated high-dose irradiation or by the direct radiation exposure on DLN. The mechanistic model successfully reproduced tumor control under various treatment conditions with appropriate parameters, indicating that it may be useful for optimizing immunoradiotherapy prescriptions. |
| format | Article |
| id | doaj-art-437dba9b1be94a9da86deac7f13d7665 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-437dba9b1be94a9da86deac7f13d76652025-08-20T02:30:45ZengNature PortfolioScientific Reports2045-23222025-06-0115111410.1038/s41598-025-04715-9Mathematical mechanistic model representing the cancer immunity cycle under radiation effectsTaisuke Takayanagi0Koichi Miyazaki1Kana Yamasaki2Takahiro Yamada3Futaro Ebina4Takahiro Kanehira5Yasuhito Onodera6Keiji Kobashi7Hiroshi Taguchi8Koichi Yasuda9Norio Katoh10Takayuki Hashimoto11Hidefumi Aoyama12Hiroki Shirato13Kenji Chamoto14Hitachi, Ltd. Research and Development GroupHitachi, Ltd. Research and Development GroupDivision of Immunology and Genomic Medicine, Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto UniversityHitachi, Ltd. Research and Development GroupHitachi, Ltd. Research and Development GroupDepartment of Medical Physics, Hokkaido University HospitalGlobal Center for Biomedical Science and Engineering, Faculty of Medicine, Hokkaido UniversityDepartment of Medical Physics, Hokkaido University HospitalDepartment of Radiation Oncology, Hokkaido University HospitalDepartment of Radiation Oncology, Faculty of Medicine, Hokkaido UniversityDepartment of Radiation Oncology, Faculty of Medicine, Hokkaido UniversityGlobal Center for Biomedical Science and Engineering, Faculty of Medicine, Hokkaido UniversityDepartment of Medical Physics, Hokkaido University HospitalGlobal Center for Biomedical Science and Engineering, Faculty of Medicine, Hokkaido UniversityDivision of Immunology and Genomic Medicine, Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto UniversityAbstract Combining radiotherapy with immune checkpoint inhibitors is a promising approach to improve the effectiveness of cancer treatment. However, the success rates of these clinical studies are limited. It is essential to determine the optimal irradiation scheme that maximizes the therapeutic effect by taking into account the balance between the positive and negative effects of radiation on immunity. In this context, we developed a mathematical mechanistic model that simulates (1) the balance between effector and exhausted cytotoxic T-lymphocytes (CTLs), (2) the number of neoantigens released by high-dose irradiation, and (3) the impact of radiation on draining lymph nodes (DLNs) for systemic anti-tumor immunity, and tested whether this mathematic model fits in several animal experiments. Our mechanistic model reproduced the anti-tumor effects of several cancer treatment models for combination therapies with radiation, immune checkpoint inhibitors, and/or a metabolic modulator. Furthermore, this mechanistic model simulated that tumor suppression in distant metastatic foci, known as the abscopal effect, was dysregulated by hypofractionated high-dose irradiation or by the direct radiation exposure on DLN. The mechanistic model successfully reproduced tumor control under various treatment conditions with appropriate parameters, indicating that it may be useful for optimizing immunoradiotherapy prescriptions.https://doi.org/10.1038/s41598-025-04715-9ImmunoradiotherapyMechanistic modelCancer-immune cycleEffector and exhausted cytotoxic T-lymphocytesHypofractionationDraining lymph node |
| spellingShingle | Taisuke Takayanagi Koichi Miyazaki Kana Yamasaki Takahiro Yamada Futaro Ebina Takahiro Kanehira Yasuhito Onodera Keiji Kobashi Hiroshi Taguchi Koichi Yasuda Norio Katoh Takayuki Hashimoto Hidefumi Aoyama Hiroki Shirato Kenji Chamoto Mathematical mechanistic model representing the cancer immunity cycle under radiation effects Scientific Reports Immunoradiotherapy Mechanistic model Cancer-immune cycle Effector and exhausted cytotoxic T-lymphocytes Hypofractionation Draining lymph node |
| title | Mathematical mechanistic model representing the cancer immunity cycle under radiation effects |
| title_full | Mathematical mechanistic model representing the cancer immunity cycle under radiation effects |
| title_fullStr | Mathematical mechanistic model representing the cancer immunity cycle under radiation effects |
| title_full_unstemmed | Mathematical mechanistic model representing the cancer immunity cycle under radiation effects |
| title_short | Mathematical mechanistic model representing the cancer immunity cycle under radiation effects |
| title_sort | mathematical mechanistic model representing the cancer immunity cycle under radiation effects |
| topic | Immunoradiotherapy Mechanistic model Cancer-immune cycle Effector and exhausted cytotoxic T-lymphocytes Hypofractionation Draining lymph node |
| url | https://doi.org/10.1038/s41598-025-04715-9 |
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