ArticleNature communications2022
CRISPR activation screen identifies BCL-2 proteins and B3GNT2 as drivers of cancer resistance to T cell-mediated cytotoxicity.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
What it found
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Who cites it
77 citing papers in PubMed, 107 citations in OpenAlex.
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- Genome-Wide CRISPR Screen Identifies a microRNA Orchestrating Pleiotropic Resistance to Targeted Therapy and T Cell Immunity in Melanoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A single-cell atlas of porcine hematopoietic development.Nature communications · 2026Article
- Context-dependent synthetic lethality - an emerging precision therapeutic approach.Nature reviews. Cancer · 2026Review
- CRISPR/Cas9 Genome Editing in Oncology: Mechanisms, Therapeutic Platforms and Translational Challenges.Molecular biotechnology · 2026Review
- CRISPR technology in ovarian cancer research: advances from gene editing to precision diagnosis and therapy.Translational cancer research · 2026Review
- High-content CRISPR activation screens identify synthetically lethal RNA-based mechanisms to sensitize cancer cells to targeted T cell cytotoxicity.Nature genetics · 2026Article
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- CD39 polymorphism enables lung thrombosis in sickle cell disease.Nature communications · 2026Article
- Multidimensional mapping of stimulation-responsive regulatory elements and candidate causal variants in T cell activation.Science advances · 2026Article
- High-throughput screening to engineer optimal T cell therapies: current knowledge and future prospects.Frontiers in oncology · 2026Review
- Shared glycosylation-related molecular mechanism and immune infiltration patterns of fetal growth restriction and preeclampsia.Frontiers in immunology · 2026Article
- Interaction between CDC6 and Tmod3 accelerates resistance to paclitaxel through focal adhesion assembly.Signal transduction and targeted therapy · 2025Article
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- Research progress in the construction and application of immunotherapy resistance models.Cancer immunology, immunotherapy : CII · 2025Review
- Genomic copy-number variants drive apoptotic evasion underlying acquired resistance to immune checkpoint inhibitors.Immunity · 2025Article
- Mini and enhanced CRISPR activators for cancer therapies.Journal of advanced research · 2025Article
- Human Synthetic Biology and Programmable Gene Regulation Control.Annual review of genomics and human genetics · 2025Review
- Multi-omic insights from a multi-ancestry genome-wide meta-analysis of ankylosing spondylitis reveal novel pathways of disease susceptibility.Research square · 2025Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The cellular processes that govern tumor resistance to immunotherapy remain poorly understood. To gain insight into these processes, here we perform a genome-scale CRISPR activation screen for genes that enable human melanoma cells to evade cytotoxic T cell killing. Overexpression of four top candidate genes (CD274 (PD-L1), MCL1, JUNB, and B3GNT2) conferred resistance in diverse cancer cell types and mouse xenografts. By investigating the resistance mechanisms, we find that MCL1 and JUNB modulate the mitochondrial apoptosis pathway. JUNB encodes a transcription factor that downregulates FasL and TRAIL receptors, upregulates the MCL1 relative BCL2A1, and activates the NF-κB pathway. B3GNT2 encodes a poly-N-acetyllactosamine synthase that targets >10 ligands and receptors to disrupt interactions between tumor and T cells and reduce T cell activation. Inhibition of candidate genes sensitized tumor models to T cell cytotoxicity. Our results demonstrate that systematic gain-of-function screening can elucidate resistance pathways and identify potential targets for cancer immunotherapy.
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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.