ArticleCell2021
Pharmacologic modulation of RNA splicing enhances anti-tumor immunity.
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Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 198 papers.
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198citing papers in PubMed
18.4field-weighted citation impact, top 1% of its field
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Who cites it
198 citing papers in PubMed, 269 citations in OpenAlex.
- Trial
- Cancers modulate processing and presentation of p53 neoantigens to evade T cell detection.Immunity · 2026Article
- Inhibition of cellular NEDDylation partially alters the MHC class I immunopeptidome.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Neoantigen cancer vaccines for gastrointestinal tumors: opportunities and challenges.MedScience · 2026Review
- Targeting PRMT5 Inhibitor-Induced Adaptation in Pancreatic Cancer with the RBM39 Degrader Indisulam.Cancer research communications · 2026Article
- Long-read sequencing reveals widespread novel splicing and neojunction-derived neoantigens in nasopharyngeal carcinoma.Genome research · 2026Article
- DRIVE: a comprehensive resource deciphering drug-induced transcriptomic and splicing response in cancer cell.Neoplasia (New York, N.Y.) · 2026Article
- Engineering editopes through programmable RNA editing toward tumor neoantigen generation.The EMBO journal · 2026Article
- HBsAg-tagged tumour vaccine system eliminates solid tumours through virus-specific memory T cells.Nature biomedical engineering · 2026Article
- Mutant TP53 hijacks RNA-splicing factor RBM28 to suppress double-stranded RNA triggered antitumor immunity.Nature communications · 2026Article
- PTBP1 controls oncogenic transcript processing and maintenance of acute myeloid leukemia.Leukemia · 2026Article
- Immune-associated alternative splicing signatures define molecular subtypes in breast cancer.iScience · 2026Article
- RNA splicing in health and disease.Molecular biomedicine · 2026Review
- Transcription Factor MAX Regulates Liver Cancer Cell Growth, Migration, Invasion, and Epithelial-Mesenchymal Transition by Promoting SF3A3 Expression.World journal of oncology · 2026Article
- CRISPR Screen Reveals Pathways and Factors Driving Tyrosine Kinase Inhibitor Resistance in Hepatocellular Carcinoma.Cancer medicine · 2026Article
- Harnessing Tumor-Specific Transcript Diversity Uncovers a Shared Neoantigen Reservoir for Pancreatic Ductal Adenocarcinoma.MedComm · 2026Article
- Targeting E3 ubiquitin ligases: Mechanistic breakthroughs and novel clinical translation pathways for tumor radioimmunotherapy.Molecular cancer · 2026Review
- An Integrative RNA Spliceosomic Landscape of Pancreatic Neuroendocrine Tumors Identifies Clinically Relevant Molecular Subgroups.Endocrine pathology · 2026Article
- Splicing-associated network PAK1-CLK1/4-SRRM1 is a vulnerability to overcome chemoresistance in human and mouse acute myeloid leukemia.Science translational medicine · 2026Article
- Splicing-driven post-translational dysregulation: a new frontier for precision cancer medicine and immunotherapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
138 more citing papers are in PubMed but not listed here.
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Authors and funding
35 authors at 11 institutions in 1 country.
Sydney X LuHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Emma De NeefComputational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
James D ThomasComputational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Erich SabioHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA; Center for Immunotherapy and Precision-Oncology, Cleveland Clinic, Cleveland, OH 44195, USA.
Benoit RousseauDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Mathieu GigouxHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA; Swim Across America and Ludwig Collaborative Laboratory, Immunology Program, Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
David A KnorrDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Benjamin GreenbaumDepartment of Epidemiology and Biostatistics, Computational Oncology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Yuval ElhanatiDepartment of Epidemiology and Biostatistics, Computational Oncology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Simon J HoggHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Andrew ChowHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA; Swim Across America and Ludwig Collaborative Laboratory, Immunology Program, Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Arnab GhoshHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA; Swim Across America and Ludwig Collaborative Laboratory, Immunology Program, Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Abigail XieMedical Scientist Training Program, Weill Cornell Medical School, New York, NY 10065, USA.
Dmitriy ZamarinHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA; Swim Across America and Ludwig Collaborative Laboratory, Immunology Program, Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Daniel CuiHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Caroline EricksonHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Michael SingerHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Hana ChoHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Eric WangHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Bin LuHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Benjamin H DurhamHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Harshal ShahHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Diego ChowellCenter for Immunotherapy and Precision-Oncology, Cleveland Clinic, Cleveland, OH 44195, USA; The Precision Immunology Institute, The Tisch Cancer Institute, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Austin M GabelComputational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Medical Scientist Training Program, University of Washington, Seattle, WA 98195, USA.
Yudao ShenMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences and Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Jing LiuMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences and Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Jian JinMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences and Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Matthew C RhodesThe Warren Family Research Center for Drug Discovery and Development and the Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
Richard E TaylorThe Warren Family Research Center for Drug Discovery and Development and the Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
Henrik MolinaProteomics Resource Center, The Rockefeller University, New York, NY 10065, USA.
Jedd D WolchokHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA; Swim Across America and Ludwig Collaborative Laboratory, Immunology Program, Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Taha MerghoubHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA; Swim Across America and Ludwig Collaborative Laboratory, Immunology Program, Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Luis A DiazDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Omar Abdel-WahabHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA. Electronic address: abdelwao@mskcc.org.
Robert K BradleyComputational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Electronic address: rbradley@fredhutch.org.
Memorial Sloan Kettering Cancer Center · USIcahn School of Medicine at Mount Sinai · USParker Institute for Cancer Immunotherapy · USFred Hutch Cancer Center · USUniversity of Notre Dame · USUniversity of Washington · USCleveland Clinic · USCornell University · USRockefeller University · USSwim Across America · USTisch Hospital · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MUniversity of Washington Medical Scientist Training Program: MD/PhDT32GM007266 · NIGMS · UNIVERSITY OF WASHINGTON · PI HORWITZ, MARSHALL S. · 1985 to 2023
$30.4MGenetic and molecular basis for SRSF2 mutations in myelodysplasiaR01HL128239 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Omar Abdel-Wahab, Robert K Bradley · 2015 to 2026
$8.0MChromosome Metabolism and Cancer Training GrantT32CA009657 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI EISENMAN, ROBERT NEIL · 1991 to 2020
$7.6MFunctional and molecular consequences of SF3B1 mutations in human hematopoietic stem cellsR01HL151651 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Robert K Bradley, Sergei Doulatov · 2020 to 2026
$4.0MInterrogating the minor spliceosome to understand and treat leukemiaR01CA251138 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ABDEL-WAHAB, OMAR, BRADLEY, ROBERT K · 2020 to 2024
$3.3MTargeting an RNA Binding Protein Network in Acute Myeloid LeukemiaR01CA242020 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ABDEL-WAHAB, OMAR, AIFANTIS, IANNIS · 2020 to 2024
$2.7MHigh-Performance Compute Cluster for Comprehensive Cancer and Infectious Diseases ResearchS10OD028685 · OD · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BRADLEY, PHILIP · 2020 to 2020
$2.0MU2AF1 mutations in myelodysplastic syndromes: from mechanism to therapyR01DK103854 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BRADLEY, ROBERT K · 2016 to 2019
$1.5MDiscovery of Selective Inhibitors for Histone MethyltransferasesR01GM122749 · NIGMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI JIN, JIAN · 2017 to 2020
$1.3MDissecting the Roles and Requirements for RBM39 in Acute Myeloid Leukemia and Normal HematopoiesisK08CA245242 · NCI · STANFORD UNIVERSITY · PI LU, SYDNEY X · 2020 to 2024
$1.2MSplicing Modulators for Rare Disease IndicationsR01GM129465 · NIGMS · UNIVERSITY OF NOTRE DAME · PI TAYLOR, RICHARD E. · 2018 to 2019
$527kNCI NIH HHS K08 CA245242NCI NIH HHS K99 CA263168NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA242020NCI NIH HHS R01 CA251138NCI NIH HHS T32 CA009657NHLBI NIH HHS R01 HL128239NHLBI NIH HHS R01 HL151651NIDDK NIH HHS R01 DK103854NIGMS NIH HHS R01 GM122749NIGMS NIH HHS R01 GM129465NIGMS NIH HHS T32 GM007266NIH HHS S10 OD028685
Abstract
Although mutations in DNA are the best-studied source of neoantigens that determine response to immune checkpoint blockade, alterations in RNA splicing within cancer cells could similarly result in neoepitope production. However, the endogenous antigenicity and clinical potential of such splicing-derived epitopes have not been tested. Here, we demonstrate that pharmacologic modulation of splicing via specific drug classes generates bona fide neoantigens and elicits anti-tumor immunity, augmenting checkpoint immunotherapy. Splicing modulation inhibited tumor growth and enhanced checkpoint blockade in a manner dependent on host T cells and peptides presented on tumor MHC class I. Splicing modulation induced stereotyped splicing changes across tumor types, altering the MHC I-bound immunopeptidome to yield splicing-derived neoepitopes that trigger an anti-tumor T cell response in vivo. These data definitively identify splicing modulation as an untapped source of immunogenic peptides and provide a means to enhance response to checkpoint blockade that is readily translatable to the clinic.
Indexed as
AnimalsAntigen PresentationAntigens, NeoplasmCell Line, TumorCell ProliferationEpitopesEthylenediaminesGene Expression Regulation, NeoplasticHematopoiesisHistocompatibility Antigens Class IHumansImmune Checkpoint InhibitorsImmunotherapyInflammationMiceMice, Inbred C57BLAntigens, NeoplasmEpitopesEthylenediaminesHistocompatibility Antigens Class IImmune Checkpoint InhibitorsMS023 compoundN-(3-chloro-7-indolyl)-1,4-benzenedisulphonamidePeptidesProtein IsoformsPyrrolesSulfonamidesimmune checkpoint blockadeimmunopeptidomeimmunotherapyneoantigensneoepitopesPD1PRMTsRBM39RNA splicingsplicing
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