ArticleNature communications2023
Leukemia-intrinsic determinants of CAR-T response revealed by iterative in vivo genome-wide CRISPR screening.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Application and prospect analysis of chimeric antigen receptor T-cell therapy in hepatocellular carcinoma treatment: a systematic review and meta-analysis.Frontiers in immunology · 2025Pooled it
- Tumor cell-intrinsic stress states drive sensitivity to CAR T cell therapy in pancreatic cancer.Science advances · 2026Article
- Physiological folate levels constrain nucleotide synthesis and increase dependence on nucleotide salvage.bioRxiv : the preprint server for biology · 2026Article
- High-Content CRISPR Screening: Methods and Applications.MedComm · 2026Review
- Challenges and advances in CAR-T cell therapy for B-ALL.Biomarker research · 2026Review
- Functional genomics for improving adoptive T-cell transfer therapies.Journal for immunotherapy of cancer · 2025Review
- NK cells mediate preventive efficacy of intravenous BCG against lung metastasis in mice.Cancer gene therapy · 2025Article
- Optimized toolkit for the manipulation of immortalized axolotl fibroblasts.Methods (San Diego, Calif.) · 2025Article
- The Paradox of Acute Myeloid Leukemia Responsiveness to Adoptive T-cell Therapy.Blood cancer discovery · 2025Article
- SOCS1 Protects Acute Myeloid Leukemia against Allogeneic T Cell-Mediated Cytotoxicity.Blood cancer discovery · 2025Article
- CAR T-cells for acute leukemias in children: current status, challenges, and future directions.Cancer metastasis reviews · 2025Review
- The Bidirectional Interplay between T Cell-Based Immunotherapies and the Tumor Microenvironment.Cancer immunology research · 2025Review
- MultiplexedbioRxiv : the preprint server for biology · 2025Article
- JAK/STAT in human diseases: a common axis in immunodeficiencies and hematological disorders.Frontiers in immunology · 2025Review
- Precision Reprogramming in CAR-T Cell Therapy: Innovations, Challenges, and Future Directions of Advanced Gene Editing.International journal of biological sciences · 2025Review
- FAS-less allogeneic CAR T cells.Nature biomedical engineering · 2024Article
- Development of an antigen-based approach to noninvasively image CAR T cells in real time and as a predictive tool.Science advances · 2024Article
- The Art of Finding the Right Drug Target: Emerging Methods and Strategies.Pharmacological reviews · 2024Review
- CRISPR-Cas and CRISPR-based screening system for precise gene editing and targeted cancer therapy.Journal of translational medicine · 2024Review
- Comprehensive characterization of IFNγ signaling in acute myeloid leukemia reveals prognostic and therapeutic strategies.Nature communications · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 5 institutions in 2 countries.
Funding
Abstract
CAR-T therapy is a promising, novel treatment modality for B-cell malignancies and yet many patients relapse through a variety of means, including loss of CAR-T cells and antigen escape. To investigate leukemia-intrinsic CAR-T resistance mechanisms, we performed genome-wide CRISPR-Cas9 loss-of-function screens in an immunocompetent murine model of B-cell acute lymphoblastic leukemia (B-ALL) utilizing a modular guide RNA library. We identified IFNγR/JAK/STAT signaling and components of antigen processing and presentation pathway as key mediators of resistance to CAR-T therapy in vivo; intriguingly, loss of this pathway yielded the opposite effect in vitro (sensitized leukemia to CAR-T cells). Transcriptional characterization of this model demonstrated upregulation of these pathways in tumors relapsed after CAR-T treatment, and functional studies showed a surprising role for natural killer (NK) cells in engaging this resistance program. Finally, examination of data from B-ALL patients treated with CAR-T revealed an association between poor outcomes and increased expression of JAK/STAT and MHC-I in leukemia cells. Overall, our data identify an unexpected mechanism of resistance to CAR-T therapy in which tumor cell interaction with the in vivo tumor microenvironment, including NK cells, induces expression of an adaptive, therapy-induced, T-cell resistance program in tumor cells.
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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.