Tailoring Chemoimmunostimulant Bioscaffolds for Inhibiting Tumor Growth and Metastasis after Incomplete Microwave Ablation.

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.