Immunogenic cell death as interplay between physical anticancer modalities and immunotherapy

Current cancer treatment strategies in practice nowadays often face limitations in effectiveness due to factors such as resistance, recurrence, or suboptimal outcomes. Traditional approaches like chemotherapy often come with severe systemic side effects due to their non-specific action, prompting the development of more targeted therapies. Among these, physical ablation techniques such as radiotherapy (RT) and focused ultrasound (FUS) have gained attention for their ability to precisely target malignant tissues, reduce physical and mental stress for the patients, and minimize recovery time. These therapies also aim to stimulate the immune system through a process referred to as immunogenic cell death (ICD), enhancing the body's ability to fight cancer, explaining abscopal effects. RT has been the most established of the abovementioned techniques for decades, and will not be included in the review. While initially focused on complete tumor ablation, these techniques are now shifting towards milder, more controlled applications that induce ICD without extensive tissue damage. This review explores how physical ablation therapies can harness ICD to boost anticancer immunity, emphasizing their potential to complement immunotherapies and improve outcomes for cancer patients.