Trigger inducible tertiary lymphoid structure formation using covalent organic frameworks for cancer immunotherapy

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 () and Zhi-Jun Sun ()
Additional contact information
Liang Zhang: Wuhan University
Boxin Zhang: Wuhan University
Meng-Jie Zhang: Wuhan University
Wenlang Li: The Hong Kong University of Science and Technology, Clear Water Bay Kowloon
Hao Li: Wuhan University
Yantian Jiao: The Hong Kong University of Science and Technology, Clear Water Bay Kowloon
Qi-Chao Yang: Wuhan University
Shuo Wang: Wuhan University
Yuan-Tong Liu: Wuhan University
An Song: Wuhan University
Hai-Tao Feng: Baoji University of Arts and Sciences
Jianwei Sun: The Hong Kong University of Science and Technology, Clear Water Bay Kowloon
Ryan T. K. Kwok: The Hong Kong University of Science and Technology, Clear Water Bay Kowloon
Jacky W. Y. Lam: The Hong Kong University of Science and Technology, Clear Water Bay Kowloon
Ben Zhong Tang: The Hong Kong University of Science and Technology, Clear Water Bay Kowloon
Zhi-Jun Sun: Wuhan University

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-024-55430-4

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