فهرست نشریات علمی دسترسی آزاد ایران

The PD-1/PD-L1 checkpoint pathway is a fundamental mechanism of immune evasion, allowing tumors to suppress T-cell activity and undermine the efficacy of immunotherapy. While monoclonal antibodies such as Avelumab block this interaction and remain the clinical standard, their effectiveness is often limited by innate or acquired resistance, high costs, and inconsistent patient responses. As an alternative, CRISPR-based genomic editing offers a transformative strategy by targeting the PD-L1 gene at its source to achieve a more durable suppression. This review evaluates advanced CRISPR techniques, including CRISPR interference (CRISPRi) for transcriptional repression, and more precise Base and Prime Editing for single-nucleotide changes, that are being deployed to eliminate PD-L1 expression in models of lung cancer, hepatocellular carcinoma, and melanoma. Studies consistently demonstrate that CRISPR-mediated PD-L1 knockdown restores T-cell-mediated cytotoxicity and leads to significant inhibition of tumor growth both in vitro and in vivo. Furthermore, combining PD-L1-edited cancer cells with CAR-T cell therapy has shown enhanced anti-tumor efficacy in solid tumor models. The precision of these approaches is now being amplified by artificial intelligence (AI), which optimizes guide RNA designs to maximize on-target efficiency and minimize off-target effects. In conclusion, CRISPR-mediated PD-L1 editing, particularly when integrated with AI-driven design, lays a robust foundation for next-generation immunotherapies. Translating this promise into clinical reality, however, hinges on overcoming persistent challenges in delivery vehicle efficiency and long-term safety profiling through ongoing investigative efforts.