Therapeutic Focused Ultrasound: Advances in Antitumor Immunotherapy of Solid Tumors

Cancer, one of the leading causes of global mortality, arises from dysregulated cellular processes that create an immunosuppressive tumor microenvironment (TME), promoting immune evasion and therapeutic resistance. While immunotherapy activates the immune system to combat tumors and provide durable benefits, its efficacy is often constrained by the hostile TME. Focused ultrasound (FUS) has emerged as a non-invasive, and precise therapeutic modality capable of mechanically or thermally ablating solid tumors. This review discusses the dual mechanisms of FUS—thermal ablation (T-HIFU) and mechanical disruption (M-HIFU, e.g., histotripsy)—and their role in modulating the TME. Specifically, it examines how FUS-induced immune activation can overcome immunosuppressive barriers, promote T-cell infiltration, and synergize with immunotherapy to improve outcomes in solid tumors, while also highlighting current challenges and future directions.