Zhou Min, Yuan Jianlong, Deng Yaqi, Fan Xianqun, Shen Jianfeng
Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200025, China.
Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, 200025, China.
Oncogenesis. 2021 Jan 8;10(1):3. doi: 10.1038/s41389-020-00296-6.
Mammalian SWI/SNF complex is a key chromatin remodeler that reshapes nucleosomes and regulates DNA accessibility. Mutations in SWI/SNF subunits are found in a broad spectrum of human cancers; however, the mechanisms of how these aberrations of SWI/SNF complex would impact tumorigenesis and cancer therapeutics remain to be elucidated. Studies have demonstrated that immune checkpoint blockade (ICB) therapy is promising in cancer treatment. Nevertheless, suitable biomarkers that reliably predict the clinical response to ICB are still lacking. Emerging evidence has suggested that SWI/SNF components play novel roles in the regulation of anti-tumor immunity, and SWI/SNF deficiency can be therapeutically targeted by ICB. These findings manifest the prominence of the SWI/SNF complex as a stratification biomarker that predicts treatment (therapeutic) response to ICB. In this review, we summarize the recent advances in ICB therapy by harnessing the cancer-specific vulnerability elicited by SWI/SNF deficiency. We provide novel insights into a comprehensive understanding of the underlying mechanisms by which SWI/SNF functions as a modulator of anti-tumor immunity.
哺乳动物的SWI/SNF复合物是一种关键的染色质重塑因子，可重塑核小体并调节DNA可及性。在多种人类癌症中都发现了SWI/SNF亚基的突变；然而，SWI/SNF复合物的这些异常如何影响肿瘤发生和癌症治疗的机制仍有待阐明。研究表明，免疫检查点阻断（ICB）疗法在癌症治疗中具有前景。尽管如此，仍然缺乏能够可靠预测对ICB临床反应的合适生物标志物。新出现的证据表明，SWI/SNF成分在抗肿瘤免疫调节中发挥着新作用，并且SWI/SNF缺陷可通过ICB进行治疗靶向。这些发现表明SWI/SNF复合物作为预测对ICB治疗反应的分层生物标志物的重要性。在本综述中，我们总结了利用SWI/SNF缺陷引发的癌症特异性脆弱性进行ICB治疗的最新进展。我们为全面理解SWI/SNF作为抗肿瘤免疫调节剂的潜在机制提供了新见解。
