ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/082/SRR26394982/SRR26394982_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/090/SRR26394990/SRR26394990_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/083/SRR26394983/SRR26394983_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/091/SRR26394991/SRR26394991_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/088/SRR26394988/SRR26394988_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/079/SRR26394979/SRR26394979_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/078/SRR26394978/SRR26394978_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/081/SRR26394981/SRR26394981_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/091/SRR26394991/SRR26394991_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/087/SRR26394987/SRR26394987_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/089/SRR26394989/SRR26394989_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/085/SRR26394985/SRR26394985_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/079/SRR26394979/SRR26394979_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/080/SRR26394980/SRR26394980_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/080/SRR26394980/SRR26394980_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/084/SRR26394984/SRR26394984_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/088/SRR26394988/SRR26394988_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/086/SRR26394986/SRR26394986_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/082/SRR26394982/SRR26394982_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/085/SRR26394985/SRR26394985_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/083/SRR26394983/SRR26394983_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/090/SRR26394990/SRR26394990_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/081/SRR26394981/SRR26394981_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/084/SRR26394984/SRR26394984_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/078/SRR26394978/SRR26394978_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/089/SRR26394989/SRR26394989_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/087/SRR26394987/SRR26394987_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/086/SRR26394986/SRR26394986_1.fastq.gzprimary200OKGenomicsThe Trustees of Columbia University in the City of New Yorkhttps://www.ebi.ac.uk/ena/browser/view/PRJNA1028533Genomic instability can trigger cancer-intrinsic innate immune responses that promote tumor rejection. However, cancer cells often evade these responses by overexpressing immune checkpoint regulators, such as PD-L1. Here, we identify the SNF2-family DNA translocase SMARCAL1 as a factor that favors tumor immune evasion by a dual mechanism involving both the suppression of innate immune signaling and the induction of PD-L1-mediated immune checkpoint responses. Mechanistically, SMARCAL1 relieves endogenous DNA damage and suppresses cGAS-STING-dependent signaling during cancer cell growth. Simultaneously, it cooperates with the AP-1 family member JUN to maintain chromatin accessibility at a transcriptional regulatory element in the PD-L1 gene, thereby promoting PD-L1 expression in cancer cells. SMARCAL1 loss hinders the ability of tumor cells to induce PD-L1 in response to genomic instability, enhances anti-tumor immune responses and sensitizes tumors to immune checkpoint blockade in a mouse melanoma model. Collectively, these studies uncover SMARCAL1 as a promising target for cancer immunotherapy. Overall design: Chromatin accessibility analysis using ATAC-seq data generated from SMARCAL1-proficient and -deficient MDA-MB-436 and B16F10 cells.xref:PubMed:38301646ENAfalseSMARCAL1 is a dual regulator of innate immune signaling and PD-L1 expression that promotes tumor immune evasion [ATAC-seq]SMARCAL1 is a dual regulator of innate immune signaling and PD-L1 expression that promotes tumor immune evasion [ATAC-seq]2025-09-242024-01-26PRJNA1028533GSE24544738301646