ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/030/SRR26394530/SRR26394530_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/017/SRR26394517/SRR26394517.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/031/SRR26394531/SRR26394531_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/026/SRR26394526/SRR26394526.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/032/SRR26394532/SRR26394532_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/020/SRR26394520/SRR26394520.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/029/SRR26394529/SRR26394529_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/029/SRR26394529/SRR26394529_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/032/SRR26394532/SRR26394532_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/024/SRR26394524/SRR26394524.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/018/SRR26394518/SRR26394518.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/022/SRR26394522/SRR26394522.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/028/SRR26394528/SRR26394528_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/033/SRR26394533/SRR26394533_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/016/SRR26394516/SRR26394516.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/027/SRR26394527/SRR26394527.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/025/SRR26394525/SRR26394525.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/021/SRR26394521/SRR26394521.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/033/SRR26394533/SRR26394533_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/028/SRR26394528/SRR26394528_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/031/SRR26394531/SRR26394531_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/030/SRR26394530/SRR26394530_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/023/SRR26394523/SRR26394523.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR263/019/SRR26394519/SRR26394519.fastq.gzprimaryOK200GenomicsThe Trustees of Columbia University in the City of New Yorkhttps://www.ebi.ac.uk/ena/browser/view/PRJNA1028535Homo sapiensGenomic 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: Gene expression profiling analysis using data from RNA-seq and plate-seq generated from SMARCAL1-proficient and -deficient MDA-MB-436 cellsxref:PubMed:38301646ENAfalseSMARCAL1 is a dual regulator of innate immune signaling and PD-L1 expression that promotes tumor immune evasion [RNA-seq]SMARCAL1 is a dual regulator of innate immune signaling and PD-L1 expression that promotes tumor immune evasion [RNA-seq]2025-09-242024-01-26PRJNA1028535GSE245449960638301646