Research Progress on the Mechanism of Anti-Tumor Immune Response Induced by TTFields

Simple Summary Although conventional and emerging treatment modalities have improved the survival outcomes of cancer patients to some extent, the prognosis for solid tumors remains notably grim. Tumor treating fields, as a novel approach for cancer therapy, have shown promising effects as both a monotherapy and in combination with chemotherapy. However, the underlying mechanisms through which TTFields exert their anticancer effects remain incompletely understood. In recent years, many researchers have suggested that inducing anti-tumor immune responses may be one of the key mechanisms of the anticancer activity of TTFields. Several clinical trials are currently exploring the combination of TTFields with tumor immunotherapy and have achieved positive results. This article reviews the research progress on the mechanisms of TTFields-induced anti-tumor immune responses and discusses their clinical significance. The objective is to offer a streamlined and precise summary to facilitate the future exploration and advancement of TTFields.Abstract Tumor treating fields (TTFields), a biophysical therapy technology that uses alternating electric fields to inhibit tumor proliferation, has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of newly diagnosed or recurrent glioblastomas (GBM) and malignant pleural mesotheliomas (MPM). Clinical trials have confirmed that TTFields are effective in slowing the tumor growth and prolonging patient survival. In recent years, many researchers have found that TTFields can induce anti-tumor immune responses, and their main mechanisms include upregulating the infiltration ratio and function of immune cells, inducing the immunogenic cell death of tumor cells, modulating immune-related signaling pathways, and upregulating the expression of immune checkpoints. Treatment regimens combining TTFields with tumor immunotherapy are emerging as a promising therapeutic approach in clinical practice. Given the increasing number of recently published studies on this topic, we provide an updated review of the mechanisms and clinical implications of TTFields in inducing anti-tumor immune responses. This review not only has important reference value for an in-depth study of the anticancer mechanism of TTFields but also provides insights into the future clinical application of TTFields.