ArticlePloS one2018
A kinetic investigation of interacting, stimulated T cells identifies conditions for rapid functional enhancement, minimal phenotype differentiation, and improved adoptive cell transfer tumor eradication.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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
11 citing papers in PubMed, 15 citations in OpenAlex.
- Mannose metabolism reshapes T cell differentiation to enhance anti-tumor immunity.Cancer cell · 2025Article
- Enhanced Immunomodulatory Effects of Thymosin-Alpha-1 in Combination with Polyanionic Carbosilane Dendrimers against HCMV Infection.International journal of molecular sciences · 2024Article
- Decrypting drug actions and protein modifications by dose- and time-resolved proteomics.Science (New York, N.Y.) · 2023Article
- Understanding the Effects of Age and T-Cell Differentiation on COVID-19 Severity: Implicating a Fas/FasL-mediated Feed-Forward Controller of T-Cell Differentiation.Frontiers in immunology · 2022Article
- Article
- Cancer immunotherapy: A comprehensive appraisal of its modes of application.Oncology letters · 2021Review
- A Critical Role for Fas-Mediated Off-Target Tumor Killing in T-cell Immunotherapy.Cancer discovery · 2021Article
- Persistence of adoptively transferred T cells with a kinetically engineered IL-2 receptor agonist.Nature communications · 2020Article
- National Cancer Institute Alliance for nanotechnology in cancer-Catalyzing research and translation toward novel cancer diagnostics and therapeutics.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2019Review
- Microchip Cytometry for Multiplexed Single-Cell Protein Detection in a Low-Resource Setting toward Point of Care Diagnosis.ACS sensors · 2018Article
- Beyond Cell Death: New Functions for TNF Family Cytokines in Autoimmunity and Tumor Immunotherapy.Trends in molecular medicine · 2018Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
For adoptive cell transfer (ACT) immunotherapy of tumor-reactive T cells, an effective therapeutic outcome depends upon cell dose, cell expansion in vivo through a minimally differentiated phenotype, long term persistence, and strong cytolytic effector function. An incomplete understanding of the biological coupling between T cell expansion, differentiation, and response to stimulation hinders the co-optimization of these factors. We report on a biophysical investigation of how the short-term kinetics of T cell functional activation, through molecular stimulation and cell-cell interactions, competes with phenotype differentiation. T cells receive molecular stimulation for a few minutes to a few hours in bulk culture. Following this priming period, the cells are then analyzed at the transcriptional level, or isolated as single cells, with continuing molecular stimulation, within microchambers for analysis via 11-plex secreted protein assays. We resolve a rapid feedback mechanism, promoted by T cell-T cell contact interactions, which strongly amplifies T cell functional performance while yielding only minimal phenotype differentiation. When tested in mouse models of ACT, optimally primed T cells lead to complete tumor eradication. A similar kinetic process is identified in CD8+ and CD4+ T cells collected from a patient with metastatic melanoma.
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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.