Engineered PD-L1 nanoregulators for enhanced tumor immunotherapy

The programmed death ligand 1 (PD-L1) pathway plays a central role in enabling tumors to escape immune detection, making it a prime target for cancer immunotherapy. While immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have shown remarkable clinical success, their therapeutic potential is constrained by significant challenges. These include immune-related opposing actions, appearance of resistance mechanisms, and inconsistent patient response rates. Addressing these limitations necessitates the development of innovative approaches to enhance treatment efficacy and safety. Nanomaterials hold considerable potential in modulating PD-L1 expression, offering advantages such as enhanced targeting precision and controlled drug delivery. In this review, we explored the impact of PD-L1 in immune evasion and its relevance to cancer immunotherapy, evaluating various nanomaterial-based approaches to regulate PD-L1 within the tumor microenvironment (TME). Additionally, we summarize and explain the potential benefits of combining these nanotechnology-based strategies with existing therapies to enhance therapeutic outcomes and deliberate the future directions for advancing nanomaterial-based approaches, as supported by preclinical and clinical evidence.