ArticleCancer discovery2022
Sequential Single-Cell Transcriptional and Protein Marker Profiling Reveals TIGIT as a Marker of CD19 CAR-T Cell Dysfunction in Patients with Non-Hodgkin Lymphoma.
Article in Cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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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
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Strategies and mechanisms for the enhancement of chimeric antigen receptor T-cell functions.Science China. Life sciences · 2026Pooled it
- CAR-T-centered sequential therapy: current status, challenges, and future clinical perspectives.Journal of hematology & oncology · 2026Review
- IFN-γ-driven iNOS induction in macrophages mediates CAR T cell resistance in B cell lymphoma.Nature communications · 2026Article
- Mapping clinical CAR-T cells: insights from scRNA-seq.Trends in molecular medicine · 2026Review
- CAR-T cell exhaustion in B cell lymphoma: Current status, mechanisms, and potential solutions.Molecular therapy. Oncology · 2026Review
- CAR-T cells with the CD38Cell reports. Medicine · 2026Article
- Mechanisms of T cell activation: Integrating signaling pathways, experimental models, and therapeutic implications.EXCLI journal · 2026Review
- Regulation of T cell exhaustion and stemness: molecular mechanisms and implications for cancer immunotherapy.Cellular & molecular immunology · 2026Review
- Integrating new and "old" cellular therapies in the evolving landscape of relapsed or refractory large B-cell lymphoma.Frontiers in oncology · 2026Review
- Preclinical evaluation of TIGIT as a target to enhance efficacy and mitigate T cell exhaustion in multiple myeloma following BCMA-CAR-T therapy.Cell death & disease · 2025Article
- Enhanced anti-liver tumor efficacy of chimeric antigen receptor-T cells via SATB1 modulation.Cell death & disease · 2025Article
- TIGIT blockade in the context of BCMA-CART cell therapy does not augment efficacy in a multiple myeloma mouse model.Oncoimmunology · 2025Article
- Acquisition of an immunosuppressive microenvironment after anti-CD19 CAR T-cell therapy is associated with T-cell dysfunction and resistance.Journal for immunotherapy of cancer · 2025Article
- Single-cell insights into the role of T cells in B-cell malignancies.FEBS letters · 2025Review
- TIGIT Affects CAR NK-cell Effector Function in the Solid Tumor Microenvironment by Modulating Immune Synapse Strength.Cancer immunology research · 2025Article
- TIGIT in cancer: from mechanism of action to promising immunotherapeutic strategies.Cell death & disease · 2025Review
- Enhancing the potency of CAR-T cells against solid tumors through transcription factor engineering.JCI insight · 2025Review
- Natural killer cell-based immunotherapy for cancer.Journal of immunology (Baltimore, Md. : 1950) · 2025Review
- SITC vision: Opportunities for deeper understanding of mechanisms of anti-tumor activity, toxicity, and resistance to optimize cancer immunotherapy.Journal for immunotherapy of cancer · 2025Article
- Two-stage CD8Nature communications · 2025Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
Abstract
Chimeric antigen receptor T-cell (CAR-T cell) therapy directed at CD19 produces durable remissions in the treatment of relapsed/refractory non-Hodgkin lymphoma (NHL). Nonetheless, many patients receiving CD19 CAR-T cells fail to respond for unknown reasons. To reveal changes in 4-1BB-based CD19 CAR-T cells and identify biomarkers of response, we used single-cell RNA sequencing and protein surface marker profiling of patient CAR-T cells pre- and postinfusion into patients with NHL. At the transcriptional and protein levels, we note the evolution of CAR-T cells toward a nonproliferative, highly differentiated, and exhausted state, with an enriched exhaustion profile in CAR-T cells of patients with poor response marked by TIGIT expression. Utilizing in vitro and in vivo studies, we demonstrate that TIGIT blockade alone improves the antitumor function of CAR-T cells. Altogether, we provide evidence of CAR-T cell dysfunction marked by TIGIT expression driving a poor response in patients with NHL. SIGNIFICANCE: This is the first study investigating the mechanisms linked to CAR-T patient responses based on the sequential analysis of manufactured and infused CAR-T cells using single-cell RNA and protein expression data. Furthermore, our findings are the first to demonstrate an improvement of CAR-T cell efficacy with TIGIT inhibition alone. This article is highlighted in the In This Issue feature, p. 1825.
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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.