ArticleCell2018
Cancer-Germline Antigen Expression Discriminates Clinical Outcome to CTLA-4 Blockade.
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Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 1 of them a synthesis that pooled it.
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112citing papers in PubMed, 1 pooled it
7.2field-weighted citation impact, top 2% of its field
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Who cites it
112 citing papers in PubMed, 1 synthesis or guideline pooled it, 170 citations in OpenAlex.
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52 more citing papers are in PubMed but not listed here.
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Authors and funding
32 authors at 12 institutions in 3 countries.
Sachet A ShuklaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute, Cambridge, MA 02142, USA.
Pavan BachireddyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute, Cambridge, MA 02142, USA; Department of Medicine, Brigham & Women's Hospital, Boston, MA 02115, USA.
Bastian SchillingDepartment of Dermatology, University Hospital, University Duisburg-Essen, 45147 Essen, Germany; German Cancer Consortium (DKTK), 69121 Heidelberg, Germany; Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, 97080 Würzburg, Germany.
Christina GalonskaMax Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
Qian ZhanProgram in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Clyde BangoDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Rupert LangerDepartment of Pathology, University of Bern, 3012 Bern, Switzerland.
Patrick C LeeDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Daniel GusenleitnerDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Derin B KeskinDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute, Cambridge, MA 02142, USA; Department of Medicine, Brigham & Women's Hospital, Boston, MA 02115, USA.
Mehrtash BabadiBroad Institute, Cambridge, MA 02142, USA.
Arman MohammadBroad Institute, Cambridge, MA 02142, USA.
Andreas GnirkeBroad Institute, Cambridge, MA 02142, USA.
Kendell ClementBroad Institute, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Zachary J CartunDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Eliezer M Van AllenDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute, Cambridge, MA 02142, USA; Department of Medicine, Brigham & Women's Hospital, Boston, MA 02115, USA.
Diana MiaoDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute, Cambridge, MA 02142, USA.
Ying HuangDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Alexandra SnyderWeill Cornell Medical College, New York, NY, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10016, USA.
Taha MerghoubWeill Cornell Medical College, New York, NY, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10016, USA.
Jedd D WolchokWeill Cornell Medical College, New York, NY, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10016, USA.
Levi A GarrawayDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute, Cambridge, MA 02142, USA; Department of Medicine, Brigham & Women's Hospital, Boston, MA 02115, USA.
Alexander MeissnerBroad Institute, Cambridge, MA 02142, USA; Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Jeffrey S WeberNew York University Langone Medical Center, New York, NY 10016, USA.
Nir HacohenBroad Institute, Cambridge, MA 02142, USA.
Donna NeubergDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Patrick R PottsDepartment of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 38105-3678, USA.
George F MurphyProgram in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Christine G LianProgram in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Dirk SchadendorfDepartment of Dermatology, University Hospital, University Duisburg-Essen, 45147 Essen, Germany; German Cancer Consortium (DKTK), 69121 Heidelberg, Germany.
F Stephen HodiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Department of Medicine, Brigham & Women's Hospital, Boston, MA 02115, USA.
Catherine J WuDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute, Cambridge, MA 02142, USA; Department of Medicine, Brigham & Women's Hospital, Boston, MA 02115, USA. Electronic address: cwu@partners.org.
Dana-Farber Cancer Institute · USHarvard University · USBrigham and Women's Hospital · USBroad Institute · USMax Planck Institute for Molecular Genetics · DEMemorial Sloan Kettering Cancer Center · USCornell University · USDeutschen Konsortium für Translationale Krebsforschung · DEGerman Cancer Research Center · DENYU Langone Health · USSt. Jude Children's Research Hospital · USUniversity of Bern · CH
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MVectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI A. Heather Eliassen · 1985 to 2026
$330.6MPersonal tumor neoantigens for immunity against chronic lymphocytic leukemiaR01CA155010 · NCI · DANA-FARBER CANCER INST · PI Catherine Ju-Ying Wu · 2011 to 2026
$9.6MPost-transplant vaccines to enhance graft-versus-leukemia responsesR01HL103532 · NHLBI · DANA-FARBER CANCER INST · PI WU, CATHERINE JU-YING · 2010 to 2013
$1.7MGeneration and characterization of tools for target-specific de novo DNA methylatR01DA036898 · NIDA · HARVARD UNIVERSITY · PI MEISSNER, ALEXANDER · 2013 to 2017
$1.7MImmunogenomic analytical approaches for research and clinical applicationsR50CA211482 · NCI · DANA-FARBER CANCER INST · PI SHUKLA, SACHET ASHOK · 2016 to 2020
$1.3MHoward Hughes Medical InstituteNCI NIH HHS P30 CA006516NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA155010NCI NIH HHS R50 CA211482NHLBI NIH HHS R01 HL103532NIDA NIH HHS R01 DA036898
Abstract
CTLA-4 immune checkpoint blockade is clinically effective in a subset of patients with metastatic melanoma. We identify a subcluster of MAGE-A cancer-germline antigens, located within a narrow 75 kb region of chromosome Xq28, that predicts resistance uniquely to blockade of CTLA-4, but not PD-1. We validate this gene expression signature in an independent anti-CTLA-4-treated cohort and show its specificity to the CTLA-4 pathway with two independent anti-PD-1-treated cohorts. Autophagy, a process critical for optimal anti-cancer immunity, has previously been shown to be suppressed by the MAGE-TRIM28 ubiquitin ligase in vitro. We now show that the expression of the key autophagosome component LC3B and other activators of autophagy are negatively associated with MAGE-A protein levels in human melanomas, including samples from patients with resistance to CTLA-4 blockade. Our findings implicate autophagy suppression in resistance to CTLA-4 blockade in melanoma, suggesting exploitation of autophagy induction for potential therapeutic synergy with CTLA-4 inhibitors.
Indexed as
Epigenesis, GeneticGerm-Line MutationAnimalsAntibodies, MonoclonalAntigens, NeoplasmAutophagyCell Line, TumorCTLA-4 AntigenDNA MethylationFemaleGene Expression ProfilingHumansImmunotherapyIpilimumabMaleMelanomaAntibodies, MonoclonalAntigens, NeoplasmCTLA-4 AntigenCTLA4 protein, humanIpilimumabMAGEA1 protein, humanMelanoma-Specific Antigensautophagycancer-germline antigencheckpoint blockadeCTLA-4immunogenomicsimmunotherapyipilimumabMAGE-AmelanomaPD-1
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