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 GSK3β, which in turn enhances PARPi-mediated PD-L1 upregulation. PARPi attenuates anticancer immunity via upregulation of PD-L1, and blockade of PD-L1 re-sensitizes PARPi-treated cancer cells to T cell killing. The combination of PARPi and anti-PD-L1 therapy compared with each agent alone significantly increased the therapeutic efficacy in vivo. In details, PARPi treatment increases T lymphocytes infiltration in tumors; however, the induced PD-L1 by PARPi on cancer cells inhibits the activation of the infiltrating T lymphocytes. Thus, the addition of PD-L1 blockade to PARPi therapy can re-activate anti-tumor immunity and improve the therapeutic efficacy. This study demonstrates a crosstalk between PARPi and tumor-associated immunosuppression, and provides a rationale for the combination of PARPi and PD-L1 or PD-1 immune checkpoint blockade as a potential therapeutic approach. (Jiao et al., 2017)
","abstract_html":"<p>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 GSK3β, which in turn enhances PARPi-mediated PD-L1 upregulation. PARPi attenuates anticancer immunity via upregulation of PD-L1, and blockade of PD-L1 re-sensitizes PARPi-treated cancer cells to T cell killing. The combination of PARPi and anti-PD-L1 therapy compared with each agent alone significantly increased the therapeutic efficacy in vivo. In details, PARPi treatment increases T lymphocytes infiltration in tumors; however, the induced PD-L1 by PARPi on cancer cells inhibits the activation of the infiltrating T lymphocytes. Thus, the addition of PD-L1 blockade to PARPi therapy can re-activate anti-tumor immunity and improve the therapeutic efficacy. This study demonstrates a crosstalk between PARPi and tumor-associated immunosuppression, and provides a rationale for the combination of PARPi and PD-L1 or PD-1 immune checkpoint blockade as a potential therapeutic approach. (Jiao et al., 2017)</p>","abstract_has_math":false,"creators":["Jiao, Shiping","0000-0001-6546-9369
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"]},{"key":"dc:title","label":"Title","values":["Parp Inhibitor Upregulates Pd-L1 Expression and Enhances Cancer-Associated Immunosuppression"]}]}],"canonical_facts":{"dc:contributor":["Mien-Chie Hung","Liuqing Yang","Jeffrey T. Chang"],"dc:creator":["Jiao, Shiping","0000-0001-6546-9369
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"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/739"],"dc:subject":["Cancer Immunotherapy; immune checkpoint; PARP inhibitor; Combination therapy","Cancer Biology","Medical Immunology","Neoplasms","Oncology"],"dc:title":["Parp Inhibitor Upregulates Pd-L1 Expression and Enhances Cancer-Associated Immunosuppression"],"thesis:degree_level":["Thesis (MS)"],"thesis:degree_name":["Masters of Science (MS)"]},"updated_at":"2026-07-24T05:50:24Z"}