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.

中文翻译：

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ARID1A缺乏症和免疫检查点封锁疗法：从机制到临床应用。

富含AT的相互作用域1A（ARID1A，也称为BAF250a）是一种染色质重塑基因，它经常在广泛的癌症中发生突变，导致ARID1A蛋白表达丢失。最近，已经报道了ARID1A缺乏与免疫检查点封锁（ICB）治疗之间的关联。ARID1A缺乏会导致高微卫星不稳定性表型，增加肿瘤突变负担，提高程序性细胞死亡配体1（PD-L1）的表达，并调节免疫微环境，从而支持ARID1A缺失可能是ICB的预测生物标志物的观点。此外，具有ARID1A缺乏症的“合成杀伤力”的治疗靶向策略表现出与ICB的潜在协同作用。