ArticleCell2019
Systematic Immunotherapy Target Discovery Using Genome-Scale In Vivo CRISPR Screens in CD8 T Cells.
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Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 204 papers.
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204citing papers in PubMed
14.9field-weighted citation impact, top 1% of its field
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Who cites it
204 citing papers in PubMed, 317 citations in OpenAlex.
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- A Comprehensive Review on CRISPR-Based Screening and Its Applications.Molecular biotechnology · 2026Review
- Segmentation-free analysis of live-cell imaging data reveals how T cell modifications influence cancer cell aggregation dynamics.Scientific reports · 2026Article
- DHX37 protein and mRNA expression patterns in breast and ovarian cancer and their prognostic implications.Histochemistry and cell biology · 2026Article
- Engineering NK and T cells with metabolite-sensing receptors to target solid tumors.Nature immunology · 2026Article
- RNA-binding proteins and ribonucleoproteins as determinants of immunity.Nature reviews. Immunology · 2026Review
- CRISPR-Cas9-mediated uATG introduction in the 5'UTR of the Uox gene for hyperuricemia mouse models: implications for gout and metabolic disorders.Science China. Life sciences · 2026Article
- DHX37 and tumor growth: a novel avenue for melanoma research.Journal of translational medicine · 2026Article
- Application of extracellular vesicles in the CRISPR-based diagnosis and treatment: possibilities and challenges.Journal of biological engineering · 2026Review
- Mitophagy and Immune Infiltration in Primary Sjögren's Disease: Insights from Bioinformatics Analysis.International journal of molecular sciences · 2026Article
- Real-time multimodal phenotyping reveals distinct tumour cell dynamics and immune escape mechanisms in T cell therapies.Nature biomedical engineering · 2026Article
- Emerging CRISPR Approaches for Countering Immune Evasion: Insight from Recent Studies.International journal of molecular sciences · 2026Review
- The opportunities and barriers for developing tumour-infiltrating lymphocyte therapy for patients with advanced genitourinary cancers.Nature reviews. Urology · 2026Review
- Efferocytosis-Driven Polyamine Metabolism in Macrophages Enhances Cancer Stem Cell Enrichment after Chemotherapy in Ovarian Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Multi-omics analysis the effects of Dhx37 deficiency on testis development and nucleolar homeostasis.Cell death discovery · 2026Article
- CRISPR-screen informed engineered T cell therapies.Frontiers in immunology · 2026Review
- High-throughput screening to engineer optimal T cell therapies: current knowledge and future prospects.Frontiers in oncology · 2026Review
- CRISPR Technology: Transforming the Future of Medicine and Diagnostics.Biochemistry · 2025Review
144 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 2 institutions in 1 country.
Matthew B DongDepartment of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; System Biology Institute, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; Yale MD-PhD Program, Yale University School of Medicine, New Haven, CT 06510, USA; Immunobiology Program, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Guangchuan WangDepartment of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; System Biology Institute, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA.
Ryan D ChowDepartment of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; System Biology Institute, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; Yale MD-PhD Program, Yale University School of Medicine, New Haven, CT 06510, USA.
Lupeng YeDepartment of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; System Biology Institute, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA.
Lvyun ZhuDepartment of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; System Biology Institute, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA.
Xiaoyun DaiDepartment of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; System Biology Institute, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA.
Jonathan J ParkDepartment of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; System Biology Institute, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; Yale MD-PhD Program, Yale University School of Medicine, New Haven, CT 06510, USA.
Hyunu R KimDepartment of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; System Biology Institute, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA.
Youssef ErramiDepartment of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; System Biology Institute, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA.
Christopher D GuzmanDepartment of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; System Biology Institute, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; Immunobiology Program, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA; Combined Program in the Biological and Biomedical Sciences, Yale University School of Medicine, New Haven, CT 06510, USA.
Xiaoyu ZhouDepartment of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; System Biology Institute, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA.
Krista Y ChenDepartment of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; System Biology Institute, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; The College, Yale University, New Haven, CT 06520, USA.
Paul A RenauerDepartment of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; System Biology Institute, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; Combined Program in the Biological and Biomedical Sciences, Yale University School of Medicine, New Haven, CT 06510, USA.
Yaying DuDepartment of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; System Biology Institute, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA.
Johanna ShenDepartment of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; System Biology Institute, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; The College, Yale University, New Haven, CT 06520, USA.
Stanley Z LamDepartment of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; System Biology Institute, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; The College, Yale University, New Haven, CT 06520, USA.
Jingjia J ZhouDepartment of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; System Biology Institute, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; The College, Yale University, New Haven, CT 06520, USA.
Donald R LanninDepartment of Surgery, Yale University School of Medicine, New Haven, CT 06510, USA; Breast Cancer Program, Yale University School of Medicine, New Haven, CT06510, USA; Smilow Cancer Hospital, 35 Park Street, New Haven, CT 06510; Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, CT 06510, USA.
Roy S HerbstDepartment of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA; Smilow Cancer Hospital, 35 Park Street, New Haven, CT 06510; Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, CT 06510, USA.
Sidi ChenDepartment of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; System Biology Institute, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Integrated Science & Technology Center, Yale University, 850 W Campus Drive, West Haven, CT 06516, USA; Yale MD-PhD Program, Yale University School of Medicine, New Haven, CT 06510, USA; Immunobiology Program, Yale University School of Medicine, New Haven, CT 06510, USA; Combined Program in the Biological and Biomedical Sciences, Yale University School of Medicine, New Haven, CT 06510, USA; Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06510, USA; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT 06510, USA; Yale Liver Center, Yale University School of Medicine, New Haven, CT 06510, USA; Yale Center for Biomedical Data Science, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address: sidi.chen@yale.edu.
Yale University · USSmilow Cancer Hospital · US
Funding
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MYale SPORE in Skin CancerP50CA121974 · NCI · YALE UNIVERSITY · PI RUTH HALABAN · 2006 to 2026
$43.9MMEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9MYale SPORE in Lung Cancer (YSILC): The Biology and Personalized Treatment of Lung CancerP50CA196530 · NCI · YALE UNIVERSITY · PI Kurt A Schalper · 2015 to 2026
$31.1MPREDOCTORAL TRAINING PROGRAM IN GENETICST32GM007499 · NIGMS · YALE UNIVERSITY · PI CARLSON, JOHN R, REINKE, VALERIE J · 1985 to 2022
$13.9MSystems analysis of phenotypic switch in control of cancer invasionU54CA209992 · NCI · YALE UNIVERSITY · PI LEVCHENKO, ANDRE · 2016 to 2021
$10.1MGENETICS AND GENOMICS OF HUMAN DISEASET32HD007149 · NICHD · YALE UNIVERSITY · PI James P Noonan · 1985 to 2026
$8.2M(PQ4) Novel tools for in vivo study of genetic interactions in cancer progressionR01CA231112 · NCI · YALE UNIVERSITY · PI CHEN, SIDI · 2018 to 2022
$3.0MHigh-throughput in vivo genetics for immunotherapy target discoveryDP2CA238295 · NCI · YALE UNIVERSITY · PI CHEN, SIDI · 2018 to 2018
$2.5MNew approaches for single cell tagging, editing and profiling of glial cells in vivoRF1DA048811 · NIDA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HONG, WEIZHE · 2019 to 2019
$2.4MRapidly scalable platforms for direct in vivo screening of functional drivers in lethal cancersR33CA225498 · NCI · YALE UNIVERSITY · PI CHEN, SIDI · 2019 to 2021
$1.2MHigh Performance Computing Instrumentation for the Yale Center for Genome AnalysiS10OD018521 · OD · YALE UNIVERSITY · PI MANE, SHRIKANT M · 2015 to 2015
$890kNCATS NIH HHS UL1 TR001863NCI NIH HHS DP2 CA238295NCI NIH HHS P50 CA121974NCI NIH HHS P50 CA196530NCI NIH HHS R01 CA231112NCI NIH HHS R33 CA225498NCI NIH HHS U54 CA209992NICHD NIH HHS T32 HD007149NIDA NIH HHS RF1 DA048811NIGMS NIH HHS T32 GM007205NIGMS NIH HHS T32 GM007499NIH HHS S10 OD018521
Abstract
CD8 T cells play essential roles in anti-tumor immune responses. Here, we performed genome-scale CRISPR screens in CD8 T cells directly under cancer immunotherapy settings and identified regulators of tumor infiltration and degranulation. The in vivo screen robustly re-identified canonical immunotherapy targets such as PD-1 and Tim-3, along with genes that have not been characterized in T cells. The infiltration and degranulation screens converged on an RNA helicase Dhx37. Dhx37 knockout enhanced the efficacy of antigen-specific CD8 T cells against triple-negative breast cancer in vivo. Immunological characterization in mouse and human CD8 T cells revealed that DHX37 suppresses effector functions, cytokine production, and T cell activation. Transcriptomic profiling and biochemical interrogation revealed a role for DHX37 in modulating NF-κB. These data demonstrate high-throughput in vivo genetic screens for immunotherapy target discovery and establishes DHX37 as a functional regulator of CD8 T cells.
Indexed as
AnimalsBreast NeoplasmsCD8-Positive T-LymphocytesCell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsCytokinesFemaleHumansImmunologic MemoryImmunotherapyMaleMiceMice, KnockoutNF-kappa BProgrammed Cell Death 1 ReceptorRNA, Guide, CRISPR-Cas SystemsCytokinesDhx37 protein, mouseNF-kappa BProgrammed Cell Death 1 ReceptorRNA, Guide, CRISPR-Cas SystemsRNA Helicasesadoptive transferbreast cancerCD8 T cellDHX37immunotherapyin vivo CRISPR screenlentiCRISPRtarget discoveryT cell effector functiontumor infiltration
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