ArticleCell2024
SMARCAL1 is a dual regulator of innate immune signaling and PD-L1 expression that promotes tumor immune evasion.
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Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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76citing papers in PubMed
18.7field-weighted citation impact, top 1% of its field
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Who cites it
76 citing papers in PubMed, 80 citations in OpenAlex.
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- Lactate-associated H3K18la upregulates RNF166 to promote immune evasion in hepatocellular carcinoma by remodeling c-Jun ubiquitination.Apoptosis : an international journal on programmed cell death · 2026Article
- High-Content CRISPR Screening: Methods and Applications.MedComm · 2026Review
- DNA Damage Response Alterations Stratify Response to ICI-Based Therapy in Advanced NSCLC with High PD-L1 Expression.Current oncology (Toronto, Ont.) · 2026Article
- Role of pyroptosis in melanoma: Molecular mechanisms and therapeutic potentials.Apoptosis : an international journal on programmed cell death · 2026Review
- SMARCAL1 is a candidate therapeutic target for ALT-positive tumors.Genes & development · 2026Article
- Multi-omics analysis of HLTF context-dependent regulation across TCGA cohorts revealed its potential as new biomarker in tumour.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- DPY30 Is an Epigenetic Decoupler Linking Replication Stress to Immunoediting in Pancreatic Cancer.Cancer research · 2026Article
- Tilting the balance of life and death: navigating DNA replication stress in cancer therapy.Experimental & molecular medicine · 2026Review
- DMAP1 Deficiency Suppresses Lung Cancer Progression by Destabilizing Replication Fork and Activating IFN Signaling-Mediated Anti-tumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Comprehensive genomics and functional analyses identifyTranslational cancer research · 2026Article
- Parallel Activation and Interference CRISPR (PAIR) with Sequencing Uncovers DNA Repair Networks Guiding Precision Cell Engineering.bioRxiv : the preprint server for biology · 2026Article
- Immune Checkpoint Inhibitors and Immunomodulators for Cancer Immunotherapy: Insights Into Resistance and Therapeutic Strategies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- WFDC21P is essential for G3BP1-mediated RIG-I activation and antitumor immunity in triple-negative breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Prognostic significance and immune correlation of STING expression and promoter methylation in renal cell carcinoma.Scientific reports · 2026Article
- Immune-evasive stem cells: engineering tolerance and reprogramming microenvironments for regenerative therapy.Stem cell research & therapy · 2026Review
- SMARCAL1 is a targetable synthetic lethal therapeutic vulnerability in ATRX-deficient gliomas that use alternative lengthening of telomeres.Neuro-oncology · 2026Article
- G3BP2-K76 acetylation promotes tumor immunoescape by stabilizing PD-L1 expression in colorectal cancer.Cell communication and signaling : CCS · 2026Article
- RF-SIRF reveals a replication stress-specific epigenetic code by spatio-temporal mapping of reversed forks.Nature communications · 2026Article
- Chromatin Accessibility in Cancer: Biological Functions, Mechanisms, Therapeutic Potential, and Future Directions.MedComm · 2026Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
33 authors at 5 institutions in 3 countries.
Giuseppe LeuzziDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Alessandro VasciaveoHerbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Angelo TaglialatelaDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Xiao ChenDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Tessa M FirestoneEpiCypher Inc., Durham, NC 27709, USA.
Allison R HickmanEpiCypher Inc., Durham, NC 27709, USA.
Wendy MaoColumbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Tanay ThakarDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Alina VaitsiankovaDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Jen-Wei HuangDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Raquel Cuella-MartinDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Samuel B HaywardDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Jordan S KesnerHerbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Ali GhasemzadehColumbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Tarun S NambiarDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Patricia HoColumbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Medicine, Division of Hematology and Oncology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Alexander RialdiCenter for OncoGenomics and Innovative Therapeutics (COGIT), Center for Therapeutics Discovery, Department of Oncological Sciences and Pharmacological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Maxime HebrardInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.
Yinglu LiDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Jinmei GaoUniversité Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198 Gif-sur-Yvette, France.
Saarang GopinathEpiCypher Inc., Durham, NC 27709, USA.
Oluwatobi A AdelekeEpiCypher Inc., Durham, NC 27709, USA.
Bryan J VentersEpiCypher Inc., Durham, NC 27709, USA.
Charles G DrakeHerbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Urology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Richard BaerHerbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Institute for Cancer Genetics, Columbia University Irving Medical Center, New York, NY 10032, USA.
Benjamin IzarHerbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Medicine, Division of Hematology and Oncology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Ernesto GuccioneCenter for OncoGenomics and Innovative Therapeutics (COGIT), Center for Therapeutics Discovery, Department of Oncological Sciences and Pharmacological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Michael-Christopher KeoghEpiCypher Inc., Durham, NC 27709, USA.
Raphael GueroisUniversité Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198 Gif-sur-Yvette, France.
Lu SunEpiCypher Inc., Durham, NC 27709, USA.
Chao LuDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Andrea CalifanoHerbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY 10032, USA.
Alberto CicciaDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Institute for Cancer Genetics, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address: ac3685@cumc.columbia.edu.
Columbia University Irving Medical Center · USEpiCypher (United States) · USCentre National de la Recherche Scientifique · FRIcahn School of Medicine at Mount Sinai · USAgency for Science, Technology and Research · SG
Funding
Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3MPredicting Cancer Cell Response to Endogenous and Exogenous Perturbations at the Single Cell LevelR35CA197745 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ANDREA CALIFANO · 2015 to 2026
$11.5MReplication fork remodeling and genomic stabilityR01CA197774 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Alberto Ciccia · 2016 to 2026
$4.2MMulti-cellular interactions defining the human brain metastatic nicheR01CA280414 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Benjamin Izar, Ashley Marie Laughney · 2023 to 2026
$2.8MMechanisms of liver metastasis and associated resistance to immunotherapyR37CA258829 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Benjamin Izar · 2021 to 2026
$2.6MEpigenetic Regulation of Head and Neck Cancer Immune EvasionR01DE031873 · NIDCR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Chao Lu · 2022 to 2026
$2.3MDevelopment of novel spike-in controls for quantitative chromatin-associated protein profilingR44DE029633 · NIDCR · EPICYPHER, INC. · PI KEOGH, MICHAEL-CHRISTOPHER, VENTERS, BRYAN J · 2019 to 2021
$2.2MRestoring genome stability and tumor suppression in BRCA1 deficient cellsR01CA227450 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BAER, RICHARD J, CICCIA, ALBERTO · 2019 to 2022
$2.1MThe role of the CD58:CD2 axis in cancer immune evasion and resistance to immunotherapyR01CA266446 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI FRANGIEH, CHRISTOPHER · 2022 to 2025
$2.0MHigh Performance Computing Cluster for Biomedical ResearchS10OD032433 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2023 to 2023
$2.0MHigh-performance compute cluster for biomedical computingS10OD012351 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2012 to 2012
$2.0MA nucleosome sliding assay platform to screen inhibitors of SWI/SNF chromatin remodeling complexesR44GM123869 · NIGMS · EPICYPHER, INC. · PI KEOGH, MICHAEL-CHRISTOPHER · 2018 to 2019
$1.7MNCI NIH HHS K99 CA273538NCI NIH HHS P30 CA013696NCI NIH HHS R01 CA197774NCI NIH HHS R01 CA227450NCI NIH HHS R01 CA266446NCI NIH HHS R01 CA280414NCI NIH HHS R35 CA197745NCI NIH HHS R37 CA258829NIDCR NIH HHS R01 DE031873NIDCR NIH HHS R44 DE029633NIGMS NIH HHS R44 GM123869NIH HHS S10 OD012351NIH HHS S10 OD020056NIH HHS S10 OD021764NIH HHS S10 OD032433
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.
Indexed as
B7-H1 AntigenDNA HelicasesImmunity, InnateMelanomaTumor EscapeAnimalsGenomic InstabilityMiceB7-H1 AntigenDNA HelicasesSmarcal1 protein, mouseAP-1cancer immunotherapycancer-intrinsic innate immunitycGAS-STING pathwayCRISPR-Cas9 screensDNA damage responseJUNPD-L1 regulationSMARCAL1
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.