Y-box Binding Protein-1 at the Crossroads of DNA Damage Response and Tumor Immune Evasion

Tumor response to radiotherapy is shaped by multiple factors including immune modulation, tumor microenvironment and genetic factors. Among these, the Y-box binding protein-1 (YB-1) is a multifunctional DNA/RNA-binding protein frequently overexpressed in tumors. YB-1 controls the activation of DNA damage response (DDR) signaling following radiotherapy. Emerging evidence suggests that the role of YB-1 extends beyond DDR regulation to shaping tumor-immune interactions by regulating cytokine production, promoting immune evasion, and altering immune checkpoint expression. Elucidating these immune-related functions of YB-1 may uncover novel mechanisms of tumor immune evasion and identify novel therapeutic targets to enhance cancer immunotherapy. This mini-review summarizes current insights into the role of YB-1 in immune regulation, highlighting its impact on tumor immunity and potential clinical applications.