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Trigger inducible tertiary lymphoid structure formation using covalent organic frameworks for cancer immunotherapy
Liang Zhang1,2, Boxin Zhang1, Meng-Jie Zhang1
1State 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 University, Wuhan, China.
Researchers developed a novel covalent organic framework (COF) to induce tertiary lymphoid structures (TLS) formation, enhancing cancer immunotherapy. This COF-mediated phototherapy effectively eradicates tumors and prevents recurrence by promoting immune cell activity.
Area of Science:
- Immunology
- Materials Science
- Oncology
Background:
- Tertiary lymphoid structures (TLS) in tumors are crucial for effective cancer immunotherapy.
- Current strategies to induce TLS formation are limited, hindering therapeutic advancements.
- Developing novel inducers for TLS formation is a significant challenge in cancer research.
Purpose of the Study:
- To explore a new method for inducing TLS formation using a covalent organic framework (COF).
- To investigate the mechanism by which COF promotes TLS formation.
- To evaluate the therapeutic efficacy of COF-mediated phototherapy in preclinical cancer models.
Main Methods:
- A novel covalent organic framework (COF) was synthesized and utilized to induce TLS formation.
- Single-cell sequencing was performed to analyze the underlying molecular mechanisms.
- COF-mediated phototherapy was tested in MC38 and 4MOSC1 female tumor models.
- Synergistic effects with αCTLA-4 immunotherapy were evaluated.
Main Results:
- The COF successfully induced TLS formation by promoting cytokine hypersecretion.
- This process facilitated T and B cell maturation, proliferation, and migration.
- COF-mediated phototherapy demonstrated efficacy in reducing tumor burden in preclinical models.
- A significant synergistic effect was observed when combined with αCTLA-4 immunotherapy, leading to tumor eradication and inhibition of recurrence.
Conclusions:
- Covalent organic frameworks represent a promising strategy for inducing TLS formation.
- COF-mediated phototherapy, especially in combination with αCTLA-4, offers a potent approach for cancer immunotherapy.
- This approach holds potential for eradicating primary and distant tumors and preventing recurrence.

