Revitalizing antitumor immunity: Leveraging nucleic acid sensors as therapeutic targets

• Published in: Cancer letters 2024-04, Vol.588, p.216729-216729, Article 216729
• Main Authors: Liu, Danfeng, He, Wei, Yang, Lei-Lei
• Format: Article
• Language: English
• Subjects: AIM2; cGAS/STING; Humans; Immunity, Innate; Immunotherapy; Interferon Type I; Neoplasms - drug therapy; Neoplasms - genetics; Nucleic acid sensors; Nucleic Acids - therapeutic use; TLRs; Tumor immunity; Tumor Microenvironment
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2024.216729

Nucleic acid sensors play a critical role in recognizing and responding to pathogenic nucleic acids as danger signals. Upon activation, these sensors initiate downstream signaling cascades that lead to the production and release of pro-inflammatory cytokines, chemokines, and type I interferons. These immune mediators orchestrate diverse effector responses, including the activation of immune cells and the modulation of the tumor microenvironment. However, careful consideration must be given to balancing the activation of nucleic acid sensors to avoid unwanted autoimmune or inflammatory responses. In this review, we provide an overview of nucleic acid sensors and their role in combating cancer through the perception of various aberrant nucleic acids and activation of the immune system. We discuss the connections between different programmed cell death modes and nucleic acid sensors. Finally, we outline the development of nucleic acid sensor agonists, highlighting how their potential as therapeutic targets opens up new avenues for cancer immunotherapy. •In this review, we provide an overview of nucleic acid sensors and their role in perceiving various aberrant nucleic acids and activating the immune system in combating cancer.•We discuss the connection between different programed cell death modes and nucleic acid sensors.•Finally, we outline the development of nucleic acid sensor agonists and their potential as therapeutic targets opens up new avenues for cancer immunotherapy.