Colloidal Hydrogel for Sensitizing Microwave Ablation‐Induced in Situ Tumor Vaccination and Modulating Innate and Adaptive Immunotherapy

Abstract Drawing inspiration from recent advances in microwave ablation (MWA) induced in situ tumor vaccination, a colloidal hydrogel comprising amphoteric gelatin nanoparticles and poly (acrylic acid) (PAA)‐calcium carbonate nanorods (PAA‐CaCO 3 NRs) is developed to deliver the microwave‐sensitive agent sodium fluoride (NaF) which can also act as a glycolysis inhibitor in conjunction with the blockade of the T‐cell Ig and ITIM domain (TIGIT), a coinhibitory receptor expressed by both natural killer (NK) cells and T cells. The combination of NaF with microwave (MW) thermal‐dynamic sensitization effectively reversed the acidic and immunosuppressive tumor microenvironment (TME). Moreover, the incorporation of anti‐TIGIT monoclonal antibody (aTIGIT) molecules amplified both the innate and adaptive immune responses by counteracting the exhaustion of NK and effective CD8 + T cells. This augmentation resulted in enhanced tumor elimination and suppression of tumor metastasis and recurrence. Thus, this study underscores the potential of colloidal hydrogel‐sensitized MWA therapy, in conjunction with aTIGIT treatments, as a promising clinical strategy for in situ cancer vaccination.