Emerging Biomaterials Blocking PD‐1/PD‐L1 Pathway for Cancer Therapy

ABSTRACT Conventional monoclonal antibodies targeting either PD‐1 or PD‐L1, despite the clinical significance as immune checkpoint inhibitors (ICIs), exhibit limited effect in the majority of cancer patients. The persistent challenges in ICIs have prompted extensive research into next‐generation biomaterial‐based immunotherapeutic strategies to inhibit PD‐1/PD‐L1 pathway. Herein, this review started with the retrospect of recent insights into the dynamic regulation of PD‐L1 expression patterns and its multifaceted functional mechanisms within the tumor microenvironment. Subsequently, the emerging alternatives to PD‐1/PD‐L1 inhibitors are summarized by their categories, including peptides, nucleic acids, small molecule inhibitors, and natural compounds, which could function by reducing PD‐L1 expression, degrading PD‐L1, or inhibiting PD‐1/PD‐L1 interactions. Furthermore, recent efforts on combination therapy based on these biomaterials are discussed, especially those with chemotherapy, radiotherapy, phototherapy, and sonodynamic therapy. This paradigm shift in PD‐1/PD‐L1 immune checkpoint blockade therapy underscores the prospects of emerging biomaterials in orchestrating anticancer immune responses, which would provide insights for developing next‐generation immunotherapeutic strategies for clinical oncology to improve patient outcomes.