{Reference Type}: Journal Article
{Title}: PTIR1 acts as an isoform of DDX58 and promotes tumor immune resistance through activation of UCHL5.
{Author}: Song J;Liu Y;Yin Y;Wang H;Zhang X;Li Y;Zhao X;Zhang G;Meng X;Jin Y;Lu D;Yin Y;
{Journal}: Cell Rep
{Volume}: 42
{Issue}: 11
{Year}: 2023 11 28
暂无{DOI}: 10.1016/j.celrep.2023.113388
{Abstract}: Cancer evades host immune surveillance by virtue of poor immunogenicity. Here, we report an immune suppressor, designated as PTIR1, that acts as a promotor of tumor immune resistance. PTIR1 is selectively induced in human cancers via alternative splicing of DDX58 (RIG-I), and its induction is closely related to poor outcome in patients with cancer. Through blocking the recruitment of leukocytes, PTIR1 facilitates cancer immune escape and tumor-intrinsic resistance to immunotherapeutic treatments. Unlike RIG-I, PTIR1 is capable of binding to the C terminus of UCHL5 and activates its ubiquitinating function, which in turn inhibits immunoproteasome activity and limits neoantigen processing and presentation, consequently blocking T cell recognition and attack against cancer. Moreover, we find that the adenosine deaminase ADAR1 induces A-to-I RNA editing on DDX58 transcript, thus triggering PTIR1 production. Collectively, our data uncover the immunosuppressive role of PTIR1 in tumorigenesis and propose that ADAR1-PTIR1-UCHL5 signaling is a potential cancer immunotherapeutic target.