ArticleProceedings of the National Academy of Sciences of the United States of America2021
Activation of NF-κB and p300/CBP potentiates cancer chemoimmunotherapy through induction of MHC-I antigen presentation.
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Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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70citing papers in PubMed
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Who cites it
70 citing papers in PubMed, 97 citations in OpenAlex.
- CREBBP loss drives immune evasion by epigenetically silencing STING and MHC-I in small cell lung cancer.Science advances · 2026Article
- ATR inhibition induces NF-κB-dependent immunogenicity in Merkel cell carcinoma independent of cGAS-STING.NPJ precision oncology · 2026Article
- LARS2 reprograms mitochondrial metabolism and epigenetically upregulates MHC-I to boost antitumor immunity in nasopharyngeal carcinoma.Journal for immunotherapy of cancer · 2026Article
- Chenodeoxycholic acid restrains tumor growth via TGR5-dependent type 1 dendritic cells cross-priming.Signal transduction and targeted therapy · 2026Article
- Plasticity of Non-Apoptotic Residual Tumor Cells After Neoadjuvant Immunochemotherapy: Epigenetic and Microenvironmental Determinants.Biomolecules · 2026Review
- Advances in Mechanism of Action and Efficacy of CBP/p300 Inhibitors in Different Subtypes of Breast Cancer.Molecules (Basel, Switzerland) · 2026Review
- Immunogenic cell death as a cornerstone for combination therapies with immune checkpoint blockade.Molecular cancer · 2026Review
- Targeted inhibition of Nrf2 potentiates antitumor immunity and enhances the efficacy of immunotherapy in hepatocellular carcinoma.Journal for immunotherapy of cancer · 2026Article
- Mitophagy-driven multidimensional regulation of tumor immune evasion and context-dependent therapeutic strategies.Journal of translational medicine · 2026Review
- Immunoregulatory roles of post-translational modifications in colorectal cancer: mechanisms and therapeutic implications.Cellular and molecular life sciences : CMLS · 2025Review
- Epigenetic drugs in cancer therapy: mechanisms, immune modulation, and therapeutic applications.Molecular biomedicine · 2025Review
- CLOCK-mediated acetylation of NF-κB p65 drives immune evasion in breast cancer.Biology direct · 2025Article
- Turning cold tumors into hot tumors to ignite immunotherapy.Molecular cancer · 2025Review
- CBP/p300, a promising therapeutic target for prostate cancer.Journal of translational medicine · 2025Review
- Novel tryptophan 2,3-dioxygenase-targeted ruthenium(ii)-indole complex activates immunotherapyChemical science · 2025Article
- Elucidating DNA Damage-Dependent Immune System Activation.International journal of molecular sciences · 2025Review
- NOTCH1 inhibition enhances immunogenicity and sensitizes triple-negative breast cancer to immune checkpoint inhibitors.Breast cancer research : BCR · 2025Article
- Oxygen vacancy-engineered bimetallic nanozymes for disrupting electron transport chain and synergistic multi-enzyme activity to reverse oxaliplatin resistance in colorectal cancer.Journal of nanobiotechnology · 2025Article
- Blocking WNT7A Enhances MHC-I Antigen Presentation and Enhances the Effectiveness of Immune Checkpoint Blockade Therapy.Cancer immunology research · 2025Article
- Cancer vaccines: current status and future directions.Journal of hematology & oncology · 2025Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
33 authors at 8 institutions in 4 countries.
Yixuan ZhouDepartment of Pharmacology, School of Medicine, University of California San Diego, CA 92093.
Ingmar Niels BastianDepartment of Pharmacology, School of Medicine, University of California San Diego, CA 92093.
Mark D LongDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263.ORCID 0000-0003-1120-8176
Michelle DowDivision of Medical Genetics, Health Sciences, Department of Biomedical Informatics, University of California San Diego, La Jolla, CA 92093.
Weihua LiDepartment of Pharmacology, School of Medicine, University of California San Diego, CA 92093.
Tao LiuDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263.ORCID 0000-0002-8818-8313
Rachael Katie NguDepartment of Pharmacology, School of Medicine, University of California San Diego, CA 92093.
Laura AntonucciDepartment of Pharmacology, School of Medicine, University of California San Diego, CA 92093.ORCID 0000-0002-3659-7334
Jian Yu HuangDepartment of Pharmacology, School of Medicine, University of California San Diego, CA 92093.
Qui T PhungDepartment of Microchemistry, Proteomics, and Lipidomics, Genentech, Inc., South San Francisco, CA 94080.ORCID 0000-0001-6472-4567
Xi-He ZhaoDepartment of Pharmacology, School of Medicine, University of California San Diego, CA 92093.
Sourav BanerjeeDepartment of Pharmacology, School of Medicine, University of California San Diego, CA 92093.ORCID 0000-0003-2043-2989
Xue-Jia LinDepartment of Pharmacology, School of Medicine, University of California San Diego, CA 92093.
Hongxia WangState Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 100850 Beijing, China.ORCID 0000-0002-9820-9261
Brian DangDepartment of Pharmacology, School of Medicine, University of California San Diego, CA 92093.
Sylvia ChoiDepartment of Pharmacology, School of Medicine, University of California San Diego, CA 92093.ORCID 0000-0003-4316-1333
Daniel KarinDepartment of Pharmacology, School of Medicine, University of California San Diego, CA 92093.
Hua SuDepartment of Pharmacology, School of Medicine, University of California San Diego, CA 92093.ORCID 0000-0003-2344-3886
Mark H EllismanNational Center for Microscopy and Imaging Research, Center for Research in Biological Systems, University of California San Diego, La Jolla, CA 92093.
Christina JamiesonDepartment of Urology, Moores Cancer Center, University of California San Diego, La Jolla, CA 92093.
Marcus BosenbergDepartment of Immunobiology, Yale School of Medicine, New Haven, CT 06510.
Zhang ChengCenter for Epigenomics, Department of Cellular and Molecular Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093.ORCID 0000-0003-3863-2866
Johannes HaybaeckInstitute of Pathology, Medical University of Graz, A-8036 Graz, Austria.ORCID 0000-0001-5518-3359
Lukas KennerDepartment of Pathology, Christian Doppler Laboratory, Medical University of Vienna, 1090 Vienna, Austria.
Kathleen M FischCenter for Computational Biology and Bioinformatics, Department of Medicine, University of California San Diego, La Jolla, CA 92093.ORCID 0000-0002-0117-7444
Richard BourgonDepartment of Cancer Immunology, Genentech, Inc., South San Francisco, CA 94080.
Genevive HernandezDepartment of Cancer Immunology, Genentech, Inc., South San Francisco, CA 94080.
Jennie R LillDepartment of Microchemistry, Proteomics, and Lipidomics, Genentech, Inc., South San Francisco, CA 94080.ORCID 0000-0002-7142-253X
Song LiuDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263.
Hannah CarterDivision of Medical Genetics, Health Sciences, Department of Biomedical Informatics, University of California San Diego, La Jolla, CA 92093.
Ira MellmanDepartment of Cancer Immunology, Genentech, Inc., South San Francisco, CA 94080.ORCID 0000-0002-6132-7299
Michael KarinDepartment of Pharmacology, School of Medicine, University of California San Diego, CA 92093; mkarin@ucsd.edu sshalapour@mdanderson.org.ORCID 0000-0002-2758-6473
Shabnam ShalapourDepartment of Pharmacology, School of Medicine, University of California San Diego, CA 92093; mkarin@ucsd.edu sshalapour@mdanderson.org.ORCID 0000-0002-4743-3706
University of California San Diego · USRoswell Park Comprehensive Cancer Center · USInnsbruck Medical University · ATNational Center of Biomedical Analysis · CNThe University of Texas MD Anderson Cancer Center · USUniversity of Dundee · GBUniversity of Veterinary Medicine Vienna · ATYale University · US
Funding
UC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3MThe Southernearch Center for ALPD and CirrhosisP50AA011999 · NIAAA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Keigo Machida · 1999 to 2026
$45.8MTumor Assessment CoreP01CA128814 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI STERN, DAVID F · 2009 to 2020
$19.1MIVEM and Image Analysis ResourceP41GM103412 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ELLISMAN, MARK H · 2012 to 2019
$17.9MSan Diego Biomedical Informatics Education & Research (SABER)T15LM011271 · NLM · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHAMIM NEMATI · 2012 to 2026
$9.7MImmuno-Oncology Translation Network: Data Management and Resource-Sharing Center at RPCIU24CA232979 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI HUTSON, ALAN DAVID, LIU, SONG · 2018 to 2024
$8.9MREGULATION OF NFKB AND IKK BY PROINFLAMMATORY STIMULIR01AI043477 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KARIN, MICHAEL · 1998 to 2017
$7.4MNF-kappaB and Mitochondrial Signals as Positive and Negative Regulators of InflammationR37AI043477 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Michael Karin · 2018 to 2026
$6.0MImmunosuppressive mechanisms responsible for development of non-viral liver cancer and control of its response to immune checkpoint inhibitorsU01AA027681 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI EL-KHOUEIRY, ANTHONY BOUTROS, KARIN, MICHAEL · 2018 to 2022
$3.6MRole of p62/SQSTM1 in obesity-induced liver cancerR01CA211794 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KARIN, MICHAEL, MOSCAT, JORGE · 2017 to 2021
$3.6MThe National Center for Microscopy and Imaging Research, a Community-wide Scientific ResourceR24GM137200 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ELLISMAN, MARK H · 2020 to 2022
$3.0MNetwork approaches to identify cancer drivers from high-dimensional tumor dataDP5OD017937 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CARTER, HANNAH KATHRYN · 2013 to 2017
$1.9MNCATS NIH HHS UL1 TR001442NCI NIH HHS P01 CA128814NCI NIH HHS R01 CA211794NCI NIH HHS U24 CA232979NIAAA NIH HHS P50 AA011999NIAAA NIH HHS U01 AA027681NIAID NIH HHS R01 AI043477NIAID NIH HHS R37 AI043477NIGMS NIH HHS P41 GM103412NIGMS NIH HHS R24 GM137200NIH HHS DP5 OD017937NIH HHS S10 OD021784NLM NIH HHS T15 LM011271
Abstract
Many cancers evade immune rejection by suppressing major histocompatibility class I (MHC-I) antigen processing and presentation (AgPP). Such cancers do not respond to immune checkpoint inhibitor therapies (ICIT) such as PD-1/PD-L1 [PD-(L)1] blockade. Certain chemotherapeutic drugs augment tumor control by PD-(L)1 inhibitors through potentiation of T-cell priming but whether and how chemotherapy enhances MHC-I-dependent cancer cell recognition by cytotoxic T cells (CTLs) is not entirely clear. We now show that the lysine acetyl transferases p300/CREB binding protein (CBP) control MHC-I AgPPM expression and neoantigen amounts in human cancers. Moreover, we found that two distinct DNA damaging drugs, the platinoid oxaliplatin and the topoisomerase inhibitor mitoxantrone, strongly up-regulate MHC-I AgPP in a manner dependent on activation of nuclear factor kappa B (NF-κB), p300/CBP, and other transcription factors, but independently of autocrine IFNγ signaling. Accordingly, NF-κB and p300 ablations prevent chemotherapy-induced MHC-I AgPP and abrogate rejection of low MHC-I-expressing tumors by reinvigorated CD8
Indexed as
AnimalsAntigen PresentationAntineoplastic AgentsApoptosisB7-H1 AntigenBiomarkers, TumorCD8-Positive T-LymphocytesCell ProliferationDrug Therapy, CombinationGene Expression Regulation, NeoplasticHistocompatibility Antigens Class IHumansImmune Checkpoint InhibitorsImmunotherapyMiceNeoplasmsAntineoplastic AgentsB7-H1 AntigenBiomarkers, TumorCD274 protein, humanHistocompatibility Antigens Class IImmune Checkpoint InhibitorsNF-kappa BOxaliplatinp300-CBP Transcription Factorsantigen presentationhistone acetylationimmune checkpoint inhibitorsMHC-INF-κB
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