Open AccessRegulation of programmed death‐ligand 1 expression in response to DNA damage in cancer cells: Implications for precision medicine
Author(s) -
Sato Hiro,
Jeggo Penny A.,
Shibata Atsushi
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14197
Subject(s) - pd l1 , dna damage , cancer , programmed cell death , cancer cell , immune system , cancer research , biomarker , ligand (biochemistry) , immunotherapy , radiation therapy , immunology , receptor , medicine , biology , apoptosis , dna , biochemistry
Anti‐programmed death‐1 ( PD ‐1)/programmed death‐ligand 1 ( PD ‐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 PD ‐1 on CTLs. Anti‐ PD ‐1/ PD ‐L1 Abs inhibit interactions between PD ‐1 and PD ‐L1 to restore antitumor immunity. Although certain patients achieve effective responses to anti‐ PD ‐1/ PD ‐L1 therapy, the efficacy of treatment is highly variable. Clinical trials of anti‐ PD ‐1/ PD ‐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‐ PD ‐1/ PD ‐L1 therapy, PD ‐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 PD ‐L1 expression levels. Therefore, understanding the mechanisms underlying the regulation of PD ‐L1 expression in cancer cells, particularly the mechanism of PD ‐L1 expression following DNA damage, is important. In this review, we consider recent findings on the regulation of PD ‐L1 expression in response to DNA damage signaling in cancer cells.