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

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.