PARP inhibitor radiosensitization enhances anti-PD-L1 immunotherapy through stabilizing chemokine mRNA in small cell lung cancer.

ABSTRACT: Immunotherapy (IO) is an effective treatment for various cancers; however, the benefits are modest for small cell lung cancer (SCLC). The poor response of SCLC to anti-PD-1/PD-L1 IO is due in part to the lack of cytotoxic T cells because of limited chemokine expression from SCLC tumors. Immunogenic radiosensitizers that enhance chemokine expression may be a promising strategy forward. Here, we show that the PARP inhibitors (PARPi), including olaparib, talazoparib and veliparib, in combination with radiotherapy (RT) enhance the immune activation and anti-tumor efficacy in SCLC cell lines, patient-derived xenograft (PDX) and syngeneic mouse models. The effect is further enhanced by continued delivery of adjuvant PARPi. The combination treatment (PARPi with RT) activates the cGAS-STING pathwa

SUBMITTER: Ran X 

PROVIDER: S-EPMC11880360 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature