ArticleThe Journal of clinical investigation2016
Memory T cell-driven differentiation of naive cells impairs adoptive immunotherapy.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers, 1 of them a synthesis that pooled it.
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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
163 citing papers in PubMed, 1 synthesis or guideline pooled it, 245 citations in OpenAlex.
- Systematic review and quantitative meta-analysis of age-dependent human T-lymphocyte homeostasis.Frontiers in immunology · 2025Pooled it
- ReducingCancer immunology research · 2018Trial
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- PD-1 protects expanding human T cells from premature restimulation-induced cell death by modulating TCR and CD28 signaling.Cell death & disease · 2026Article
- Single-cell transcriptome analysis reveals the potential heterogeneous mechanism of CD8Scientific reports · 2025Article
- CAR-engineered lymphocyte persistence is governed by a FAS ligand-FAS autoregulatory circuit.Nature cancer · 2025Article
- Mechanisms of Resistance to CAR T-Cells and How to Overcome Them.Methods and protocols · 2025Review
- Beneficial effect of resveratrol on T cell oxidative metabolism and anti-tumor function is conditioned by priorMolecular therapy. Methods & clinical development · 2025Article
- CD95/Fas stoichiometry in future precision medicine.Cell death and differentiation · 2025Review
- Resistance Mechanisms to BCMA Targeting Bispecific Antibodies and CAR T-Cell Therapies in Multiple Myeloma.Cells · 2025Review
- Co-expression of IL-15 and CCL21 strengthens CAR-NK cells to eliminate tumors in concert with T cells and equips them with PI3K/AKT/mTOR signal signature.Journal for immunotherapy of cancer · 2025Article
- Biomaterial-Based Therapeutic Delivery of Immune Cells.Advanced healthcare materials · 2025Review
- Recent advancements in improving the efficacy and safety of chimeric antigen receptor (CAR)-T cell therapy for hepatocellular carcinoma.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Novel Assignment of Gene Markers to Hematological and Immune Cells Based on Single-Cell Transcriptomics.International journal of molecular sciences · 2025Article
- Immunosenescence, Physical Exercise, and their Implications in Tumor Immunity and Immunotherapy.International journal of biological sciences · 2025Review
- MFAP4 is a novel prognostic biomarker in glioma correlating with immunotherapy resistance and ferroptosis.Frontiers in pharmacology · 2025Article
- Rapidly Manufactured CAR-T with Conserved Cell Stemness and Distinctive Cytokine-Secreting Profile Shows Improved Anti-Tumor Efficacy.Vaccines · 2024Article
- Integrated single-cell transcriptome and TCR profiles of hepatocellular carcinoma highlight the convergence on interferon signaling during immunotherapy.Journal for immunotherapy of cancer · 2024Article
- Functionalized nanowires for miRNA-mediated therapeutic programming of naïve T cells.Nature nanotechnology · 2024Article
- Metabolic dialogues: regulators of chimeric antigen receptor T cell function in the tumor microenvironment.Molecular oncology · 2024Review
103 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 5 institutions in 2 countries.
Funding
Abstract
Adoptive cell transfer (ACT) of purified naive, stem cell memory, and central memory T cell subsets results in superior persistence and antitumor immunity compared with ACT of populations containing more-differentiated effector memory and effector T cells. Despite a clear advantage of the less-differentiated populations, the majority of ACT trials utilize unfractionated T cell subsets. Here, we have challenged the notion that the mere presence of less-differentiated T cells in starting populations used to generate therapeutic T cells is sufficient to convey their desirable attributes. Using both mouse and human cells, we identified a T cell-T cell interaction whereby antigen-experienced subsets directly promote the phenotypic, functional, and metabolic differentiation of naive T cells. This process led to the loss of less-differentiated T cell subsets and resulted in impaired cellular persistence and tumor regression in mouse models following ACT. The T memory-induced conversion of naive T cells was mediated by a nonapoptotic Fas signal, resulting in Akt-driven cellular differentiation. Thus, induction of Fas signaling enhanced T cell differentiation and impaired antitumor immunity, while Fas signaling blockade preserved the antitumor efficacy of naive cells within mixed populations. These findings reveal that T cell subsets can synchronize their differentiation state in a process similar to quorum sensing in unicellular organisms and suggest that disruption of this quorum-like behavior among T cells has potential to enhance T cell-based immunotherapies.
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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.