Silencing PD-1 and PD-L1 with Nanoparticle-Delivered Small Interfering RNA Increases Cytotoxicity of Tumor-Infiltrating Lymphocytes

AIM: To determine if silencing PD-1 on tumor-infiltrating lymphocytes (TILs) and its ligand-1 (PD-L1) on cancer cells will enhance the cytotoxicity of TILs. MATERIALS & METHODS: Lipid-coated calcium phosphate nanoparticles were synthesized to deliver siRNAs against PD-1 and PD-L1 to TILs and breast cancer MCF-7 cells. The downregulation of PD-1/PD-L1 expressions was determined by real-time PCR and western blotting assays. The killing efficacy of TILs to MCF-7 cells was determined by cytotoxic T lymphocyte assay. RESULTS: Lipid-coated calcium phosphate nanoparticles effectively delivered siRNAs and silenced PD-1 and PD-L1sh expression. The knockdown of either gene or both greatly improved the cytotoxicity of TILs. CONCLUSION: Silencing PD-1 and PD-L1 is an effective approach to increase TIL cytotoxicity to cancer cells.