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

The discovery of tertiary lymphoid structures (TLS) within the tumor tissues provides a promising avenue to promote the response rate of cancer immunotherapy. Yet, the lack of effective strategies to promote 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 frameworks (COFs) was employed to promote the formation of TLS. Single-cell sequencing analysis revealed that this was achieved by promoting the cytokine hypersecretion to facilitate the maturation, proliferation, and migration of T and B cells, critical for trigger TLS formation. Furthermore, the high efficacy of COF-mediated phototherapy in inducing TLS formation was validated in both the MC38 and 4MOSC1 tumor models. Moreover, an efficient synergism between COF-mediated phototherapy and αCTLA-4 was observed, which was able to effectively eradicate both primary and distant tumors, and inhibit tumor recurrence. This study underscores a new approach of boosting cancer immunotherapy through COF triggered TLS formation. Overall design: Tumor tissues from 4T1 tumor-bearing mice that had undergone AIE COF-mediated phototherapy and those that had not received AIE COF-mediated phototherapy