ArticleNature communications2024
CAR affinity modulates the sensitivity of CAR-T cells to PD-1/PD-L1-mediated inhibition.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 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
- Covalently PD-L1 Anchoring Drives Bispecific Nanostructure Assembly for Spatial Control of T Cell Recruitment and Activation.Angewandte Chemie (International ed. in English) · 2026Article
- Chimeric antigen receptor (CAR)-T cell therapy for solid tumors in pediatric patients: current breakthroughs, dilemmas, and strategies.Experimental hematology & oncology · 2026Review
- Supramolecular immunomodulatory hydrogelator potentiates CAR-T therapy with long-lasting endogenous immunity toward solid tumor eradication.Science advances · 2026Article
- Investigating the role of costimulatory domains in enhancing CAR-T cell persistence in TNBC.Cancer gene therapy · 2026Review
- Multiple Myeloma Cells Resistant to T-cell Therapies Exhibit a CD45+ Immunoevasive Phenotype.Cancer immunology research · 2026Article
- Engineering a PD-L1-sensing synthetic receptor for programmable macrophage response.Journal of biological engineering · 2026Article
- Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.Journal of translational medicine · 2026Review
- Nanoparticle Strategies for Bone Metastasis Immunotherapy: Targeting, Immune Reprogramming and Combination Therapy.Pharmaceutics · 2026Review
- MUC1-targeted CAR-T cell secreted anti-PD-1 IgG antibody enhances antitumor activity in Cholangiocarcinoma.Scientific reports · 2026Article
- CAR-T cell therapy in breast cancer management: expanding horizon and overcoming challenges beyond hematologic cancers.Molecular biology reports · 2026Review
- Arming oncolytic herpes simplex virus with CXCL-11, IL-12 and a single-chain antibody against PD-1 to enhance CAR-T cell therapy in pancreatic ductal adenocarcinoma.Cell death & disease · 2026Article
- Bridging biomaterials and immunotherapy: hydrogel strategies for next-generation CAR-T cell treatment.Stem cell research & therapy · 2026Review
- Lung tumouroids as a testing platform for precision CAR T cell therapy.Nature biomedical engineering · 2026Article
- Article
- Measuring the Degree of Labeling of Antibody-Dye Conjugates with a Single-Molecule-Sensitive Digital Flow Cytometer.Analytical chemistry · 2026Article
- Integrating CAR-T therapy with PD-1/PD-L1 blockade: Mechanisms, synergy, and optimized strategies in NSCLC.iScience · 2026Review
- TIPE2 knockdown enhances the anti-tumor efficacy of NKG2D CAR-T cells against pancreatic cancer via activating NF-κb signaling pathway.Journal of translational medicine · 2026Article
- Obstacles and improvement strategies for CAR-T cell therapy in solid tumors.Discover oncology · 2026Review
- Advancing adoptive T cell therapy in ovarian cancer: barriers, innovations, and emerging platforms.Journal for immunotherapy of cancer · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Chimeric antigen receptor (CAR)-T cell therapy for solid tumors faces significant hurdles, including T-cell inhibition mediated by the PD-1/PD-L1 axis. The effects of disrupting this pathway on T-cells are being actively explored and controversial outcomes have been reported. Here, we hypothesize that CAR-antigen affinity may be a key factor modulating T-cell susceptibility towards the PD-1/PD-L1 axis. We systematically interrogate CAR-T cells targeting HER2 with either low (LA) or high affinity (HA) in various preclinical models. Our results reveal an increased sensitivity of LA CAR-T cells to PD-L1-mediated inhibition when compared to their HA counterparts by using in vitro models of tumor cell lines and supported lipid bilayers modified to display varying PD-L1 densities. CRISPR/Cas9-mediated knockout (KO) of PD-1 enhances LA CAR-T cell cytokine secretion and polyfunctionality in vitro and antitumor effect in vivo and results in the downregulation of gene signatures related to T-cell exhaustion. By contrast, HA CAR-T cell features remain unaffected following PD-1 KO. This behavior holds true for CD28 and ICOS but not 4-1BB co-stimulated CAR-T cells, which are less sensitive to PD-L1 inhibition albeit targeting the antigen with LA. Our findings may inform CAR-T therapies involving disruption of PD-1/PD-L1 pathway tailored in particular for effective treatment of solid tumors.
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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.