Emerging role of SWI/SNF complex deficiency as a target of immune checkpoint blockade in human cancers

Abstract

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.