Dynamic Tumor Immunology-on-a-Chip for Peripheral Blood-Derived Tumor-Reactive T Cell Expansion
Adoptive T cell therapy has shown great promise in the treatment of solid tumors, which, however, poses a great challenge to obtain autologous tumor-reactive T cells in a cost-effective manner. Here, we present a dynamic tumor immunology-on-a-chip, mimicking immune responses, for achieving the enric...
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| Language: | English |
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American Association for the Advancement of Science (AAAS)
2025-01-01
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| Series: | Research |
| Online Access: | https://spj.science.org/doi/10.34133/research.0639 |
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| author | Xin Shou Yunru Yu Dan Wu Peihua Lu Miaoqing Zhao Yuanjin Zhao |
| author_facet | Xin Shou Yunru Yu Dan Wu Peihua Lu Miaoqing Zhao Yuanjin Zhao |
| author_sort | Xin Shou |
| collection | DOAJ |
| description | Adoptive T cell therapy has shown great promise in the treatment of solid tumors, which, however, poses a great challenge to obtain autologous tumor-reactive T cells in a cost-effective manner. Here, we present a dynamic tumor immunology-on-a-chip, mimicking immune responses, for achieving the enrichment and expansion of tumor-reactive T cells. Tumor spheroids with uniform size can be generated by seeding tumor cells in hydrogel-embedded micropillar arrays, and could be trapped upon removal of hydrogel. Then, T cells were infused and fully contacted with these tumor spheroids under biomimetic flow conditions provided by herringbone-patterned microgrooves arrays. We found that the tamed tumor-reactive T cells could be fully activated and a rapid clonal proliferation was realized during the cultivation. In addition, these tumor-reactive T cells exhibited a specific and powerful tumor-killing capability in vitro. Thus, the suggested dynamic microfluidic chips with staged structure-transformable properties realize both the producible formation of tumor spheroids and the recapitulation of tumor-immune crosstalk to expand tumor-reactive T cells. These features indicate that the dynamic and reproducible tumor immunology-on-a-chip has potential in the preparation of therapeutic T cell products for clinical cancer immunotherapy. |
| format | Article |
| id | doaj-art-820eea00c59e4e31bb7e0fb493a0e8c1 |
| institution | Kabale University |
| issn | 2639-5274 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Research |
| spelling | doaj-art-820eea00c59e4e31bb7e0fb493a0e8c12025-08-20T03:48:26ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742025-01-01810.34133/research.0639Dynamic Tumor Immunology-on-a-Chip for Peripheral Blood-Derived Tumor-Reactive T Cell ExpansionXin Shou0Yunru Yu1Dan Wu2Peihua Lu3Miaoqing Zhao4Yuanjin Zhao5Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Institute of Translational Medicine, Shulan International Medical College, Zhejiang Shuren University, Hangzhou 310015, China.Department of Oncology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi 214023, China.Department of Pathology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, China.Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.Adoptive T cell therapy has shown great promise in the treatment of solid tumors, which, however, poses a great challenge to obtain autologous tumor-reactive T cells in a cost-effective manner. Here, we present a dynamic tumor immunology-on-a-chip, mimicking immune responses, for achieving the enrichment and expansion of tumor-reactive T cells. Tumor spheroids with uniform size can be generated by seeding tumor cells in hydrogel-embedded micropillar arrays, and could be trapped upon removal of hydrogel. Then, T cells were infused and fully contacted with these tumor spheroids under biomimetic flow conditions provided by herringbone-patterned microgrooves arrays. We found that the tamed tumor-reactive T cells could be fully activated and a rapid clonal proliferation was realized during the cultivation. In addition, these tumor-reactive T cells exhibited a specific and powerful tumor-killing capability in vitro. Thus, the suggested dynamic microfluidic chips with staged structure-transformable properties realize both the producible formation of tumor spheroids and the recapitulation of tumor-immune crosstalk to expand tumor-reactive T cells. These features indicate that the dynamic and reproducible tumor immunology-on-a-chip has potential in the preparation of therapeutic T cell products for clinical cancer immunotherapy.https://spj.science.org/doi/10.34133/research.0639 |
| spellingShingle | Xin Shou Yunru Yu Dan Wu Peihua Lu Miaoqing Zhao Yuanjin Zhao Dynamic Tumor Immunology-on-a-Chip for Peripheral Blood-Derived Tumor-Reactive T Cell Expansion Research |
| title | Dynamic Tumor Immunology-on-a-Chip for Peripheral Blood-Derived Tumor-Reactive T Cell Expansion |
| title_full | Dynamic Tumor Immunology-on-a-Chip for Peripheral Blood-Derived Tumor-Reactive T Cell Expansion |
| title_fullStr | Dynamic Tumor Immunology-on-a-Chip for Peripheral Blood-Derived Tumor-Reactive T Cell Expansion |
| title_full_unstemmed | Dynamic Tumor Immunology-on-a-Chip for Peripheral Blood-Derived Tumor-Reactive T Cell Expansion |
| title_short | Dynamic Tumor Immunology-on-a-Chip for Peripheral Blood-Derived Tumor-Reactive T Cell Expansion |
| title_sort | dynamic tumor immunology on a chip for peripheral blood derived tumor reactive t cell expansion |
| url | https://spj.science.org/doi/10.34133/research.0639 |
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