Reactive Oxygen Species– and DNA Damage Response–Dependent NK Cell Activating Ligand Upregulation Occurs at Transcriptional Levels and Requires the Transcriptional Factor E2F1

摘要: Increasing evidence indicates that cancer cell stress induced by chemotherapeutic agents promote antitumor immune responses and contribute to their full clinical efficacy. In this article, we identify the signaling events underlying chemotherapy-induced NKG2D DNAM-1 ligand expression on multiple myeloma (MM) cells. Our findings indicate sublethal doses of doxorubicin melphalan initiate a DNA damage response (DDR) controlling upregulation MM lines patient-derived malignant plasma cells in Chk1/2-dependent p53-independent manner. Drug-induced MICA PVR gene are transcriptionally regulated involve DDR-dependent E2F1 transcription factor activity. We also describe involvement changes redox state control surface transcriptional activity using antioxidant agent N-acetyl-L-cysteine. Finally, accordance with much indicating DDR oxidative major determinants cellular senescence, found redox-dependent activation upon treatment is critical for entry premature senescence required preferential senescent cells, which preferentially killed NK trigger potent IFN-γ production. propose immunogenic as mechanism promotes clearance drug-treated tumor innate effector lymphocytes, including