ArticleNature genetics2021
Multimodal pooled Perturb-CITE-seq screens in patient models define mechanisms of cancer immune evasion.
Article in Nature genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 166 papers.
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Who cites it
166 citing papers in PubMed, 252 citations in OpenAlex.
- Single-cell Transcriptomics in Autoimmune Diseases: Mechanistic Insights, Cross-disease Convergence, and Translational Challenges in Rheumatoid Arthritis, Systemic Lupus Erythematosus, Type 1 Diabetes, and Multiple Sclerosis.Clinical reviews in allergy & immunology · 2026Review
- CRISPR in clinical oncology: translational advances from molecular diagnostics to therapeutics.Nature reviews. Clinical oncology · 2026Review
- A systematic comparison of single-cell perturbation response prediction models.Science advances · 2026Article
- PredictedInternational journal of molecular sciences · 2026Article
- CRISPR-cas systems in pharmacology: functional pharmacogenomics, drug screening, resistance, and therapeutic translation.Functional & integrative genomics · 2026Review
- From Cluster to Claim: Calibrating Interpretation in Single-Cell Transcriptomics.Advanced genetics (Hoboken, N.J.) · 2026Article
- Targeting GLUTs in Cancer: Mechanisms, Combination Strategies, and Translational Challenges.Current medical science · 2026Review
- scGPA: an LLM-assisted workflow for directional virtual gene perturbation analysis from single-cell transcriptomes.BMC genomics · 2026Article
- A pre-trained large generative model for translating single-cell transcriptomes to proteomes.Nature biomedical engineering · 2026Article
- Single-Cell CRISPR: An Efficient Strategy for Decoding Plant Cis-Regulatory Complexity.Plant biotechnology journal · 2026Review
- ScalablebioRxiv : the preprint server for biology · 2026Article
- Systema: a framework for evaluating genetic perturbation response prediction beyond systematic variation.Nature biotechnology · 2026Article
- Spurious correlation inflates performance in single-cell perturbation prediction.bioRxiv : the preprint server for biology · 2026Article
- CRISPR Screening in Hepatocellular Carcinoma: From Tumor Progression to Immune Evasion and Therapeutic Resistance.International journal of molecular sciences · 2026Review
- Integrating Spatial Proteogenomics in Cancer Research.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Advancing single-cell omics and cell-based therapeutics with quantum computing.Nature reviews. Molecular cell biology · 2026Review
- Disordered protein LAT encodes relative levels of signaling pathways in T cell activation.Science (New York, N.Y.) · 2026Article
- Single-cell and spatial profiling in cancer biology and clinical oncology.Nature cancer · 2026Review
- High-content CRISPR activation screens identify synthetically lethal RNA-based mechanisms to sensitize cancer cells to targeted T cell cytotoxicity.Nature genetics · 2026Article
- DUSP6 ablation restores CAR T-cell fitness impaired by tumor CD58 loss through invigoration of AP-1 signaling.Signal transduction and targeted therapy · 2026Article
106 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 6 institutions in 2 countries.
Funding
Abstract
Resistance to immune checkpoint inhibitors (ICIs) is a key challenge in cancer therapy. To elucidate underlying mechanisms, we developed Perturb-CITE-sequencing (Perturb-CITE-seq), enabling pooled clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 perturbations with single-cell transcriptome and protein readouts. In patient-derived melanoma cells and autologous tumor-infiltrating lymphocyte (TIL) co-cultures, we profiled transcriptomes and 20 proteins in ~218,000 cells under ~750 perturbations associated with cancer cell-intrinsic ICI resistance (ICR). We recover known mechanisms of resistance, including defects in the interferon-γ (IFN-γ)-JAK/STAT and antigen-presentation pathways in RNA, protein and perturbation space, and new ones, including loss/downregulation of CD58. Loss of CD58 conferred immune evasion in multiple co-culture models and was downregulated in tumors of melanoma patients with ICR. CD58 protein expression was not induced by IFN-γ signaling, and CD58 loss conferred immune evasion without compromising major histocompatibility complex (MHC) expression, suggesting that it acts orthogonally to known mechanisms of ICR. This work provides a framework for the deciphering of complex mechanisms by large-scale perturbation screens with multimodal, single-cell readouts, and discovers potentially clinically relevant mechanisms of immune evasion.
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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.