ArticleCancer research2023
Systematic Interrogation of Tumor Cell Resistance to Chimeric Antigen Receptor T-cell Therapy in Pancreatic Cancer.
Article in Cancer research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
19 citing papers in PubMed, 26 citations in OpenAlex.
- Tumor cell-intrinsic stress states drive sensitivity to CAR T cell therapy in pancreatic cancer.Science advances · 2026Article
- High-Content CRISPR Screening: Methods and Applications.MedComm · 2026Review
- Advances, challenges, and innovative strategies of CAR-T cell therapy in pancreatic cancer.Biomarker research · 2026Review
- CRISPR/Cas9 in perspective: evaluating efficacy, delivery methods, and ethical challenges in genome editing.Molecular biology reports · 2026Review
- Article
- Senescence-associated LncRNAs TRMP and TRMP-S promote gastric cancer by activating IGFL4.Scientific reports · 2026Article
- Radiotherapy as a partner for immunotherapy in pancreatic cancer: current landscape and future directions.Frontiers in oncology · 2026Review
- High-throughput screening to engineer optimal T cell therapies: current knowledge and future prospects.Frontiers in oncology · 2026Review
- CRISPR/Cas technologies in pancreatic cancer research and therapeutics: recent advances and future outlook.Discover oncology · 2025Review
- New developments in immunotherapy for SCLC.Journal for immunotherapy of cancer · 2025Review
- The present and future of the Cancer Dependency Map.Nature reviews. Cancer · 2025Review
- The power and the promise of CAR-mediated cell immunotherapy for clinical application in pancreatic cancer.Journal of advanced research · 2025Review
- Leveraging CRISPR gene editing technology to optimize the efficacy, safety and accessibility of CAR T-cell therapy.Leukemia · 2024Review
- High-throughput screening for optimizing adoptive T cell therapies.Experimental hematology & oncology · 2024Review
- Comprehensive Analysis and Verification of the Prognostic Significance of Cuproptosis-Related Genes in Colon Adenocarcinoma.International journal of molecular sciences · 2024Article
- Protein lipidation in health and disease: molecular basis, physiological function and pathological implication.Signal transduction and targeted therapy · 2024Review
- A stumbling block in pancreatic cancer treatment: drug resistance signaling networks.Frontiers in cell and developmental biology · 2024Review
- CD8Frontiers in immunology · 2024Review
- Advancements in CRISPR screens for the development of cancer immunotherapy strategies.Molecular therapy oncolytics · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Chimeric antigen receptor (CAR) T-cell therapy can lead to dramatic clinical responses in B-cell malignancies. However, early clinical trials with CAR T-cell therapy in non-B-cell malignancies have been disappointing to date, suggesting that tumor-intrinsic features contribute to resistance. To investigate tumor-intrinsic modes of resistance, we performed genome scale CRISPR-Cas9 screens in mesothelin (MSLN)-expressing pancreatic cancer cells. Co-culture with MSLN-targeting CAR T cells identified both antigen-dependent and antigen-independent modes of resistance. In particular, loss of the majority of the genes involved in the pathway responsible for GPI-anchor biosynthesis and attachment abrogated the ability of CAR T cells to target pancreatic cancer cells, suggesting that disruption of this pathway may permit MSLN CAR T-cell evasion in the clinic. Antigen-independent mediators of CAR T-cell response included members of the death receptor pathway as well as genes that regulate tumor transcriptional responses, including TFAP4 and INTS12. TFAP4-mediated CAR T resistance depended on the NFκB transcription factor p65, indicating that tumor resistance to CAR T-cell therapy likely involves alterations in tumor-intrinsic states. Overall, this study uncovers multiple antigen-dependent and -independent mechanisms of CAR T-cell evasion by pancreatic cancer, paving the way for overcoming resistance in this disease that is notoriously refractory to immunotherapy. SIGNIFICANCE: The identification and validation of key determinants of CAR T-cell response in pancreatic cancer provide insights into the landscape of tumor cell intrinsic resistance mechanisms and into approaches to improve therapeutic efficacy.
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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.