ArticleMolecular cancer therapeutics2023
T Cell-intrinsic Immunomodulatory Effects of TAK-981 (Subasumstat), a SUMO-activating Enzyme Inhibitor, in Chronic Lymphocytic Leukemia.
Article in Molecular cancer therapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 15 citations in OpenAlex.
- SUMO2 deletion changes chromatin accessibility and enhances cytotoxic T cell activation and tumor infiltration.Science advances · 2026Article
- SUMOylation in cancer: molecular mechanisms and therapeutic implications.Molecular cancer · 2026Review
- Post-Translational Regulation of CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Targeting SUMOylation Triggers IFN-β-dependent Activation of Patient and Allogenic NK Cells in Preclinical Models of Acute Myeloid Leukemia.Molecular cancer therapeutics · 2026Article
- Post-translational modifications at the crossroads of cancer metabolism and immune regulation: therapeutic opportunities and challenges.International journal of surgery (London, England) · 2026Review
- Mild microwave hyperthermia promotes mitotic catastrophe, induces time-delayed cGAS-STING activation and restores sensitivity to anti-PDL1 therapy in Pan02 pancreatic cancer model.Oncoimmunology · 2025Article
- Targeting SUMOylation promotes cBAF complex stabilization and disruption of the SS18::SSX transcriptome in synovial sarcoma.Nature communications · 2025Article
- Immune regulation by the SUMO family.Nature reviews. Immunology · 2025Review
- Quantitation of TAK-981 in human plasma via LC-MS/MS and its application in clinical trials.Bioanalysis · 2025Article
- Comprehensive SUMO Proteomic Analyses Identify HIV Latency-Associated Proteins in Microglia.Cells · 2025Article
- Regulation of the immune microenvironment by SUMO in diabetes mellitus.Frontiers in immunology · 2025Review
- Review
- Positioning SUMO as an immunological facilitator of oncolytic viruses for high-grade glioma.Frontiers in cell and developmental biology · 2023Review
- Safety and biologic activity of a canine anti-CD20 monoclonal antibody in dogs with diffuse large B-cell lymphoma.Journal of veterinary internal medicineArticle
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Novel targeted agents used in therapy of lymphoid malignancies are recognized to have complex immune-mediated effects. Sumoylation, a posttranslational modification of target proteins by small ubiquitin-like modifiers (SUMO), regulates a variety of cellular processes indispensable in immune cell activation. Despite this, the role of sumoylation in T-cell biology in context of cancer is not known. TAK-981 (subasumstat) is a small-molecule inhibitor of the SUMO-activating enzyme (SAE) that forms a covalent adduct with an activated SUMO protein. Using T cells derived from patients with chronic lymphocytic leukemia (CLL), we demonstrate that targeting SAE activates type I IFN response. This is accompanied by largely intact T-cell activation in response to T-cell receptor engagement, with increased expression of CD69 and CD38. Furthermore, TAK-981 decreases regulatory T cell (Treg) differentiation and enhances secretion of IFNγ by CD4+ and CD8+ T cells. These findings were recapitulated in mouse models, suggesting an evolutionarily conserved mechanism of T-cell activation regulated by SUMO modification. Relevant to the consideration of TAK-981 as an effective agent for immunotherapy in hematologic malignancies, we demonstrate that the downstream impact of TAK-981 administration is enhancement of the cytotoxic function of CD8+ T cells, thus uncovering immune implications of targeting sumoylation in lymphoid neoplasia.
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Registered trials
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 OpenQuestion graph.