Regulation of programmed death‐ligand 1 expression in response to DNA damage in cancer cells: Implications for precision medicine

摘要

Anti‐programmed death‐1 ( ‐1)/programmed death‐ligand 1 ( ‐L1) therapy, which is one of the most promising cancer therapies, is licensed for treating various tumors. Programmed death‐ligand 1, which is expressed on the surface of cancer cells, leads to the inhibition of T lymphocyte activation and immune evasion if it binds to the receptor ‐1 on CTLs. Anti‐ ‐1/ ‐L1 Abs inhibit interactions between ‐1 and ‐L1 to restore antitumor immunity. Although certain patients achieve effective responses to anti‐ ‐1/ ‐L1 therapy, the efficacy of treatment is highly variable. Clinical trials of anti‐ ‐1/ ‐L1 therapy combined with radiotherapy/chemotherapy are underway with suggestive evidence of favorable outcome; however, the molecular mechanism is largely unknown. Among several molecular targets that can influence the efficacy of anti‐ ‐1/ ‐L1 therapy, ‐L1 expression in tumors is considered to be a critical biomarker because there is a positive correlation between the efficacy of combined treatment protocols and ‐L1 expression levels. Therefore, understanding the mechanisms underlying the regulation of ‐L1 expression in cancer cells, particularly the mechanism of ‐L1 expression following damage, is important. In this review, we consider recent findings on the regulation of ‐L1 expression in response to damage signaling in cancer cells.