Figure 6.

Immune effects and potential therapeutic strategies using DEE microspheres loaded with immune-modulating agents with or without vascular modulators. Clinically approved drugs as well as novel immune modulators (bottom left) can be delivered in combination with locoregional therapies (top left). This potentially includes TACE in which the immune modulators may be loaded into DEE microspheres as a novel treatment paradigm in HCC. The hypothesis is that intra-arterial delivery of these drugs using DEE microspheres may reduce systemic toxicities, provide greater control over drug spatio-temporal distribution, and promote local immunologic effects initiated by TACE. For example, antigens and cell debris generated by TACE or other locoregional therapies can accumulate in the tumor microenvironment (top right) and trigger a cascade of immunologic events, promoted by immune-modulating agents delivered locally at the site, that include recruitment of immune cells and cytokine release ultimately leading to promotion of antitumor immune responses (bottom right). (RFA: radiofrequency ablation; MWA: microwave ablation; IRE: irreversible electroporation; HIFU: high intensity focused ultrasound; TAE: transarterial embolization)