Affiliation:
1. Tongji Hospital
2. University of Science and Technology
Abstract
Abstract
Lung adenocarcinoma (LUAD) is the most common pathological subtype of non-small cell lung cancer. Although the application of immune checkpoint inhibitors has greatly improved the therapy of solid tumors, treatment of lots of patients with lung adenocarcinoma is still not satisfactory. For most diseases with low immunogenicity, it’s urgent to seek for new combination treatment strategies.
Platinum is a widely used DNA damage agent. PARP inhibitors are more effective for tumors with defects in DNA damage and repair. In the context of inhibition of PARP1, tumor cells are easier to form more immunogenic tumor antigen libraries and increase immunogenicity. Nonetheless, the efficacy of PARP inhibitors, combined with platinum and immune checkpoint inhibitors is still undefined. In this research, we have demonstrated that inhibiting PARP1 activated cGAS-STING pathway to up-regulate PD-L1 expression in lung adenocarcinoma cells by real-time quantitative PCR and immunoblotting. Then, we constructed a LLC tumor model to verify that PARP inhibitors, combined with platinum and immune checkpoint inhibitors could change the lymphocyte infiltration in tumor microenvironment, increase the proportion of CD8+T cells and activated DC cells, and enhance anti-tumor immunity.
To sum up, we confirmed that PARP inhibitors combined with platinum can enhance the immune checkpoint effect by activating cGAS-STING pathway, further increase the infiltration of CD8+ T and DC cells and reshape tumor immune microenvironment. Therefore, this research provides a novel strategy for the treatment of lung adenocarcinoma patients with poor prognosis.
Publisher
Research Square Platform LLC