Tailoring Chemoimmunostimulant Bioscaffolds for Inhibiting Tumor Growth and Metastasis after Incomplete Microwave Ablation
Yuting Shen, Liang Chen, Xin Guan, Xiaoxia Han, Xiao‐Wan Bo, Shaoyue Li, Liping Sun, Yu Chen, Wenwen Yue, Hui‐Xiong Xu
Abstract
Microwave ablation has attracted the most attention as a locoregional therapeutic method for solid neoplasms. However, the high incidence of incomplete ablation that could promote the rapid cancer progression still remains a challenge in clinic. Herein, we found that the high invasiveness of residual tumor following incomplete microwave ablation (iMWA) is mainly due to the myeloid cell-mediated immunosuppression. Accordingly, we develop a biohydrogel scaffold-enabled chemoimmunotherapeutic strategy by targeting myeloid cells with a phosphoinositide 3-kinase γ (PI3Kγ) inhibitor (IPI549) to synergize with immunostimulatory chemotherapy (Oxaliplatin, OX) for post-ablative cancer therapy. With several tumor mouse models, we reveal that OX&IPI549@Gel-based localized chemoimmunotherapy can substantially suppress the growth of tumor post-iMWA, simultaneously evoke robust systemic anticancer immunity to inhibit metastatic spread, and offer strong long-term immunological memory functions against tumor rechallenge. Besides, this work proposes a potential opportunity for precision medicine by utilizing a mechanism-based rationale to the adoption of our pre-existing arsenal of anticancer immunotherapeutic schedule.