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. Tumor tissues from 4T1 tumor-bearing mice that had undergone AIE COF-mediated phototherapy and those that had not received AIE COF-mediated phototherapy