看完这篇Cell系列综述，你就能理解自身免疫疾病与癌症免疫疗法的下一个风口

Core Viewpoint - The article discusses the dual role of ADAR1 protein in maintaining immune balance and its involvement in cancer progression, highlighting the potential for developing ADAR1 inhibitors for cancer treatment [3][12]. Group 1: ADAR1 Functionality - ADAR1 is an RNA editing enzyme that converts adenosine (A) to inosine (I) in double-stranded RNA (dsRNA), which is recognized as guanosine (G), thus facilitating RNA-level gene editing [5]. - There are two isoforms of ADAR1: ADAR1p110, which is involved in basic RNA editing and cellular homeostasis, and ADAR1p150, which is induced by interferons and plays a critical role in suppressing excessive immune activation [5]. Group 2: ADAR1 Deficiency and Autoimmunity - Deficiency or mutation of ADAR1, particularly the p150 isoform, can lead to severe autoimmune diseases due to the exposure of unedited endogenous dsRNA, activating various cellular sensors [8][11]. - The sensors activated include MDA5, which triggers interferon expression, and PKR, which halts global protein synthesis, potentially leading to cell death [8][9]. Group 3: ADAR1 in Cancer - ADAR1 can be exploited by cancer cells to evade immune detection by upregulating its expression, thus disguising themselves from the immune system [12]. - Inhibiting ADAR1 could expose cancer cells to immune recognition, simulating a viral infection state and activating immune responses against tumors [12]. Group 4: Development of ADAR1 Inhibitors - The article outlines six strategies for developing ADAR1 inhibitors, including accumulating dsRNA, inhibiting ADAR1's binding to dsRNA, and depleting ADAR1 through targeted degradation [15][16]. - These strategies aim to enhance the immune system's ability to recognize and attack cancer cells by increasing the levels of unedited dsRNA [16]. Group 5: Future Directions - Ongoing research aims to clarify which specific endogenous dsRNAs are most likely to trigger autoimmune responses and to develop selective inhibitors targeting the ADAR1p150 isoform in cancer cells [19][25].