Trigger inducible tertiary lymphoid structure formation using covalent organic frameworks for cancer immunotherapy
Abstract The discovery of tertiary lymphoid structures (TLS) within tumor tissues provides a promising avenue to promote the efficacy of cancer immunotherapy. Yet, the lack of effective strategies to induce TLS formation poses a substantial obstacle. Thus, the exploration of potential inducers for T...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55430-4 |
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| author | Liang Zhang Boxin Zhang Meng-Jie Zhang Wenlang Li Hao Li Yantian Jiao Qi-Chao Yang Shuo Wang Yuan-Tong Liu An Song Hai-Tao Feng Jianwei Sun Ryan T. K. Kwok Jacky W. Y. Lam Ben Zhong Tang Zhi-Jun Sun |
| author_facet | Liang Zhang Boxin Zhang Meng-Jie Zhang Wenlang Li Hao Li Yantian Jiao Qi-Chao Yang Shuo Wang Yuan-Tong Liu An Song Hai-Tao Feng Jianwei Sun Ryan T. K. Kwok Jacky W. Y. Lam Ben Zhong Tang Zhi-Jun Sun |
| author_sort | Liang Zhang |
| collection | DOAJ |
| description | Abstract The discovery of tertiary lymphoid structures (TLS) within tumor tissues provides a promising avenue to promote the efficacy of cancer immunotherapy. Yet, the lack of effective strategies to induce TLS formation poses a substantial obstacle. Thus, the exploration of potential inducers for TLS formation is of great interest but remains challenging. Here, inspired by the mechanism of artificially cultivated pearls, a covalent organic framework (COF) is employed to induce TLS formation. Single-cell sequencing analysis reveals that this is achieved by promotion of cytokine hypersecretion, which facilitates the maturation, proliferation, and migration of T and B cells, critical for triggering TLS formation. Furthermore, the efficacy of COF-mediated phototherapy in inducing TLS formation is validated in both the MC38 and 4MOSC1 female tumor models. Notably, a strong synergistic effect between COF-mediated phototherapy and αCTLA-4 is observed, resulting in the effective eradication of both primary and distant tumors, while also inhibiting tumor recurrence. |
| format | Article |
| id | doaj-art-e3c7a3d406724fd0b5afdb9ed5cd656a |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e3c7a3d406724fd0b5afdb9ed5cd656a2025-01-05T12:38:08ZengNature PortfolioNature Communications2041-17232025-01-0116111610.1038/s41467-024-55430-4Trigger inducible tertiary lymphoid structure formation using covalent organic frameworks for cancer immunotherapyLiang Zhang0Boxin Zhang1Meng-Jie Zhang2Wenlang Li3Hao Li4Yantian Jiao5Qi-Chao Yang6Shuo Wang7Yuan-Tong Liu8An Song9Hai-Tao Feng10Jianwei Sun11Ryan T. K. Kwok12Jacky W. Y. Lam13Ben Zhong Tang14Zhi-Jun Sun15State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan UniversityDivision of Life Science and State Key Laboratory of Molecular Neuroscience, Department of Chemistry, The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science and Technology, Clear Water Bay KowloonState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan UniversityDivision of Life Science and State Key Laboratory of Molecular Neuroscience, Department of Chemistry, The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science and Technology, Clear Water Bay KowloonState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan UniversityAIE Research Center, College of Chemistry and Chemical Engineering, Baoji University of Arts and SciencesDivision of Life Science and State Key Laboratory of Molecular Neuroscience, Department of Chemistry, The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science and Technology, Clear Water Bay KowloonDivision of Life Science and State Key Laboratory of Molecular Neuroscience, Department of Chemistry, The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science and Technology, Clear Water Bay KowloonDivision of Life Science and State Key Laboratory of Molecular Neuroscience, Department of Chemistry, The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science and Technology, Clear Water Bay KowloonDivision of Life Science and State Key Laboratory of Molecular Neuroscience, Department of Chemistry, The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science and Technology, Clear Water Bay KowloonState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan UniversityAbstract The discovery of tertiary lymphoid structures (TLS) within tumor tissues provides a promising avenue to promote the efficacy of cancer immunotherapy. Yet, the lack of effective strategies to induce TLS formation poses a substantial obstacle. Thus, the exploration of potential inducers for TLS formation is of great interest but remains challenging. Here, inspired by the mechanism of artificially cultivated pearls, a covalent organic framework (COF) is employed to induce TLS formation. Single-cell sequencing analysis reveals that this is achieved by promotion of cytokine hypersecretion, which facilitates the maturation, proliferation, and migration of T and B cells, critical for triggering TLS formation. Furthermore, the efficacy of COF-mediated phototherapy in inducing TLS formation is validated in both the MC38 and 4MOSC1 female tumor models. Notably, a strong synergistic effect between COF-mediated phototherapy and αCTLA-4 is observed, resulting in the effective eradication of both primary and distant tumors, while also inhibiting tumor recurrence.https://doi.org/10.1038/s41467-024-55430-4 |
| spellingShingle | Liang Zhang Boxin Zhang Meng-Jie Zhang Wenlang Li Hao Li Yantian Jiao Qi-Chao Yang Shuo Wang Yuan-Tong Liu An Song Hai-Tao Feng Jianwei Sun Ryan T. K. Kwok Jacky W. Y. Lam Ben Zhong Tang Zhi-Jun Sun Trigger inducible tertiary lymphoid structure formation using covalent organic frameworks for cancer immunotherapy Nature Communications |
| title | Trigger inducible tertiary lymphoid structure formation using covalent organic frameworks for cancer immunotherapy |
| title_full | Trigger inducible tertiary lymphoid structure formation using covalent organic frameworks for cancer immunotherapy |
| title_fullStr | Trigger inducible tertiary lymphoid structure formation using covalent organic frameworks for cancer immunotherapy |
| title_full_unstemmed | Trigger inducible tertiary lymphoid structure formation using covalent organic frameworks for cancer immunotherapy |
| title_short | Trigger inducible tertiary lymphoid structure formation using covalent organic frameworks for cancer immunotherapy |
| title_sort | trigger inducible tertiary lymphoid structure formation using covalent organic frameworks for cancer immunotherapy |
| url | https://doi.org/10.1038/s41467-024-55430-4 |
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