{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Leuzzi G"],"funding":["NIDCR NIH HHS","NCI NIH HHS","NIH HHS","NIGMS NIH HHS"],"pagination":["861-881.e32"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10980358"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["187(4)"],"pubmed_abstract":["Genomic 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 limits endogenous DNA damage, thereby suppressing cGAS-STING-dependent signaling during cancer cell growth. Simultaneously, it cooperates with the AP-1 family member JUN to maintain chromatin accessibility at a PD-L1 transcriptional regulatory element, 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."],"journal":["Cell"],"pubmed_title":["SMARCAL1 is a dual regulator of innate immune signaling and PD-L1 expression that promotes tumor immune evasion."],"pmcid":["PMC10980358"],"funding_grant_id":["R44 GM123869","R01 CA266446","R35 CA197745","R01 DE031873","S10 OD012351","K99 CA273538","S10 OD032433","P30 CA013696","S10 OD020056","R01 CA197774","R37 CA258829","R01 CA227450","R44 DE029633","R01 CA280414","S10 OD021764"],"pubmed_authors":["Venters BJ","Gao J","Guccione E","Ghasemzadeh A","Sun L","Leuzzi G","Huang JW","Hickman AR","Izar B","Mao W","Baer R","Taglialatela A","Chen X","Cuella-Martin R","Rialdi A","Firestone TM","Thakar T","Nambiar TS","Gopinath S","Lu C","Ciccia A","Kesner JS","Vasciaveo A","Li Y","Keogh MC","Vaitsiankova A","Califano A","Ho P","Hayward SB","Adeleke OA","Drake CG","Hebrard M","Guerois R"],"additional_accession":[]},"is_claimable":false,"name":"SMARCAL1 is a dual regulator of innate immune signaling and PD-L1 expression that promotes tumor immune evasion.","description":"Genomic 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 limits endogenous DNA damage, thereby suppressing cGAS-STING-dependent signaling during cancer cell growth. Simultaneously, it cooperates with the AP-1 family member JUN to maintain chromatin accessibility at a PD-L1 transcriptional regulatory element, 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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2026-06-03T04:48:27.092Z","creation":"2025-04-04T00:16:13.667Z"},"accession":"S-EPMC10980358","cross_references":{"pubmed":["38301646"],"doi":["10.1016/j.cell.2024.01.008"]}}