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Dissertations & Theses (Open Access)
Cancer Immunotherapy; immune checkpoint; PARP inhibitor; Combination therapy
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Parp Inhibitor Upregulates Pd-L1 Expression And Enhances Cancer-Associated Immunosuppression, Shiping Jiao
Parp Inhibitor Upregulates Pd-L1 Expression And Enhances Cancer-Associated Immunosuppression, Shiping Jiao
Dissertations & Theses (Open Access)
With recent approvals for therapeutic antibodies that block CTLA4, PD-1 and PD-L1, immune checkpoints have emerged as new targets in cancer therapy. In addition, there is accumulating evidence highlighting the role of cancer-associated immunity in patient response to cytotoxic anticancer agents. Inhibitors of poly (ADP-ribose) polymerase (PARP) have shown substantial cytotoxic effects against tumors with defects in DNA damage responses. However, whether a crosstalk between PARP inhibition and immune checkpoints exists remains unclear. Here, it has been shown that PARP inhibitors (PARPis) upregulate PD-L1 expression in multiple cancer cell lines, human xenograft tumors, and syngeneic mouse tumors. Mechanistically, PARPi inactivates …