Senescence prostate cancer cell promotes resistance to immune checkpoint blockade through ATR activation

Background: Checkpoint blockade immunotherapy represented by PD-1/PD-L1 or CTLA4 antibody treatment, has been of tremendous success for multiple cancers. Most patients with prostate cancer (PCa) either do not respond to CTLA4 immune checkpoint blockade or develop resistance to it, often because of low CTLA4 antigen presentation in cancer cells. Conclusions: We demonstrate that senescence-related ATR activation plays a vital role in regulating CTLA4 expression and immune response of PCa, which may provide a general strategy to overcome immunotherapy resistance.