Zhang Liang, Zhang Boxin, Zhang Meng-Jie, Li Wenlang, Li Hao, Jiao Yantian, Yang Qi-Chao, Wang Shuo, Liu Yuan-Tong, Song An, Feng Hai-Tao, Sun Jianwei, Kwok Ryan T K, Lam Jacky W Y, Tang Ben Zhong, Sun Zhi-Jun
State 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.
Division 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 Kowloon, Hong Kong, China.
Nat Commun. 2025 Jan 2;16(1):44. doi: 10.1038/s41467-024-55430-4.
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.
肿瘤组织中三级淋巴结构（TLS）的发现为提高癌症免疫治疗的疗效提供了一条有前景的途径。然而，缺乏诱导TLS形成的有效策略构成了重大障碍。因此，探索TLS形成的潜在诱导剂备受关注，但仍具有挑战性。在此，受人工养殖珍珠机制的启发，采用共价有机框架（COF）来诱导TLS形成。单细胞测序分析表明，这是通过促进细胞因子的过度分泌来实现的，这有助于T细胞和B细胞的成熟、增殖和迁移，而这些对于触发TLS形成至关重要。此外，在MC38和4MOSC1雌性肿瘤模型中均验证了COF介导的光疗在诱导TLS形成方面的疗效。值得注意的是，观察到COF介导的光疗与αCTLA-4之间具有强烈的协同效应，从而有效根除原发性和远处肿瘤，同时还能抑制肿瘤复发。
