ArticleJournal for immunotherapy of cancer2019
PD-1 silencing impairs the anti-tumor function of chimeric antigen receptor modified T cells by inhibiting proliferation activity.
Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
What it found
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Who cites it
64 citing papers in PubMed, 104 citations in OpenAlex.
- PD-1 and TIGIT downregulation distinctly affect the effector and early memory phenotypes of CD19-targeting CAR T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Trial
- Chimeric antigen receptor (CAR)-T cell therapy for solid tumors in pediatric patients: current breakthroughs, dilemmas, and strategies.Experimental hematology & oncology · 2026Review
- Anti-PD-1 Nanobody-Armored MSLN CAR-T Therapy for Malignant Mesothelioma: Preclinical and Clinical Studies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Antigen spreading mediates heterogeneous solid tumor eradication by DNA demethylating agent-programmed CAR T cells.Science advances · 2026Article
- CAR-T cell exhaustion in B cell lymphoma: Current status, mechanisms, and potential solutions.Molecular therapy. Oncology · 2026Review
- Integrating CAR-T therapy with PD-1/PD-L1 blockade: Mechanisms, synergy, and optimized strategies in NSCLC.iScience · 2026Review
- Plying potency assays for immunotherapy of solid tumors.Frontiers in immunology · 2026Review
- Improving CAR T cell therapy against malignancies through gene knock-down/out strategies: a systematic review.Cancer cell international · 2025Review
- Next-generation T cell immunotherapies engineered with CRISPR base and prime editing: challenges and opportunities.Nature reviews. Clinical oncology · 2025Review
- High-Resolution Spatial Proteomics Characterises Colorectal Cancer Consensus Molecular Subtypes.bioRxiv : the preprint server for biology · 2025Article
- CAR Beyond αβ T Cells: Unleashing NK Cells, Macrophages, and γδ T Lymphocytes Against Solid Tumors.Vaccines · 2025Review
- The Potential Use of Digital Twin Technology for Advancing CAR-T Cell Therapy.Current issues in molecular biology · 2025Review
- XCL1-secreting CEA CAR-T cells enhance endogenous CD8Journal for immunotherapy of cancer · 2025Article
- Review
- PD-1 blockade does not improve efficacy of EpCAM-directed CAR T-cell in lung cancer brain metastasis.Cancer immunology, immunotherapy : CII · 2024Article
- Review
- CD5 deletion enhances the antitumor activity of adoptive T cell therapies.Science immunology · 2024Article
- Overcoming the challenges of primary resistance and relapse after CAR-T cell therapy.Expert review of clinical immunology · 2024Review
- Genetically Engineered CLDN18.2 CAR-T Cells Expressing Synthetic PD1/CD28 Fusion Receptors Produced Using a Lentiviral Vector.Journal of microbiology (Seoul, Korea) · 2024Article
- CAR affinity modulates the sensitivity of CAR-T cells to PD-1/PD-L1-mediated inhibition.Nature communications · 2024Article
4 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
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBlocking programmed death-1 (PD-1) is considered to be a promising strategy to improve T cell function, and this is being explored in many ongoing clinical trials. In fact, our knowledge about PD-1 is primarily based on the results of short-term experiments or observations, but how long-lasting PD-1 blockade can affect T cell function remains unclear.
methodsWe planned to use shRNA-based gene knockdown technology to mimic long-lasting PD-1 blockade. We constructed PD-1 steadily blocked chimeric antigen receptor modified T (CAR-T) cells, and with these cells we can clearly study the effects of PD-1 knockdown on T cell function. The anti-tumor function, proliferation ability and differentiation status of PD-1 silenced CAR-T cells were studied by in vitro and animal experiments.
resultsAccording to short-term in vitro results, it was reconfirmed that the resistance to programmed death-ligand 1 (PD-L1)-mediated immunosuppression could be enhanced by PD-1 blockade. However, better anti-tumor function was not presented by PD-1 blocked CAR-T cells in vitro or in vivo experiments. It was found that PD-1 knockdownmight impair the anti-tumor potential of CAR-T cells because it inhibited T cells' proliferation activity. In addition, we observed that PD-1 blockade would accelerate T cells' early differentiation and prevent effector T cells from differentiating into effect memory T cells, and this might be the reason for the limited proliferation of PD-1 silenced CAR-T cells.
conclusionThese results suggest that PD-1 might play an important role in maintaining the proper proliferation and differentiation of T cells, and PD-1 silencing would impair T cells' anti-tumor function by inhibiting their proliferation activity.
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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.