TY - JOUR
T1 - ARID1A deficiency and immune checkpoint blockade therapy
T2 - From mechanisms to clinical application
AU - Hu, Guangyuan
AU - Tu, Wei
AU - Yang, Liu
AU - Peng, Guang
AU - Yang, Lin
N1 - Publisher Copyright:
© 2020
PY - 2020/3/31
Y1 - 2020/3/31
N2 - The AT-rich interaction domain 1A (ARID1A, also known as BAF250a) is a chromatin remodeling gene, which frequently mutates across a broad spectrum of cancers with loss expression of the ARID1A protein. Recently, the association between ARID1A deficiency and immune checkpoint blockade (ICB) therapy has been reported. ARID1A deficiency contributes to the high microsatellite instability phenotype, increases tumor mutation burden, elevates expression of programmed cell death ligand 1 (PD-L1), and modulates the immune microenvironment, supporting the view that ARID1A loss might serve as a predictive biomarker for ICB. Furthermore, the therapeutic targeting strategies, which show “synthetic lethality” with ARID1A deficiency, exhibit potential synergy with ICB. We collectively reviewed the mechanisms underlying the correlation between ARID1A deficiency and ICB, the predictive function of ARID1A deficiency for ICB, and potential combined strategies of targeting agents, vulnerable for ARID1A deficiency, with ICB in cancer treatment.
AB - The AT-rich interaction domain 1A (ARID1A, also known as BAF250a) is a chromatin remodeling gene, which frequently mutates across a broad spectrum of cancers with loss expression of the ARID1A protein. Recently, the association between ARID1A deficiency and immune checkpoint blockade (ICB) therapy has been reported. ARID1A deficiency contributes to the high microsatellite instability phenotype, increases tumor mutation burden, elevates expression of programmed cell death ligand 1 (PD-L1), and modulates the immune microenvironment, supporting the view that ARID1A loss might serve as a predictive biomarker for ICB. Furthermore, the therapeutic targeting strategies, which show “synthetic lethality” with ARID1A deficiency, exhibit potential synergy with ICB. We collectively reviewed the mechanisms underlying the correlation between ARID1A deficiency and ICB, the predictive function of ARID1A deficiency for ICB, and potential combined strategies of targeting agents, vulnerable for ARID1A deficiency, with ICB in cancer treatment.
KW - Chromatin remodeling gene
KW - Combined therapy
KW - Immunotherapy
KW - Predictive biomarker
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U2 - 10.1016/j.canlet.2020.01.001
DO - 10.1016/j.canlet.2020.01.001
M3 - Review article
C2 - 31911080
AN - SCOPUS:85077655562
SN - 0304-3835
VL - 473
SP - 148
EP - 155
JO - Cancer Letters
JF - Cancer Letters
ER -