New therapies targeting the PD1/PDL-1 pathway for lung cancer

Abstract

Lung cancer is giving promising results in immunotherapy treatments, even though it is one of the cancers with worse prognosis. Silencing of the PD1 / PDL-1 pathway is one of the most widely used strategies for this type of cancer. This pathway is usually found to be overexpressed in lung cancer; it should be noted that it helps tumor cells to evade the anti-tumor response of the immune system. PPRHs are DNA molecules used for gene silencing. They were recently discovered and have been previously tested in other types of cancer to modulate the PD1 / PDL-1 pathway. During the present research project, the main objective was to validate the PPRHs strategy to inhibit the PD1/PDL-1 pathway as a possible treatment of pulmonary adenocarcinoma. THP-1 cells were differentiated to macrophages with PMA. Different PPRHs against PD1 and PDL-1 were designed and tested in THP-1 and A549 cell lines, first separately, testing for cross toxicity and then in co-culture. Cell viability was assessed by MTT assays. Differentiation of THP-1 to macrophages showed no significant differences at three different concentrations of PMA. Cross-toxicity assays showed a decrease in cell viability when transfecting A549 cells with PPRHs against PD1, whereas this effect was not observed in THP-1 transfected with PPRHS against PDL-1. Co-culture experiment showed that the combination of PPRHs against PD1 and PDL-1 produced an enhancement of the antitumor effect, compared to their individual effects separately. Our results support the usage of PPRHs for the silencing PD1/PDL-1 pathway in lung cancer.