ArticleCell2016
A Distinct Gene Module for Dysfunction Uncoupled from Activation in Tumor-Infiltrating T Cells.
Article in Cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 277 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
277 citing papers in PubMed, 1 synthesis or guideline pooled it, 427 citations in OpenAlex.
- Interpretation of T cell states from single-cell transcriptomics data using reference atlases.Nature communications · 2021Pooled it
- Blockade of LAG-3 and PD-1 leads to co-expression of cytotoxic and exhaustion gene modules in CD8Cell · 2024Trial
- Innovations and emerging trends in adoptive cell therapies for solid tumors: engineering strategies and clinical translation.Experimental hematology & oncology · 2026Review
- A modular synthetic promoter toolkit for programmable gene control in activated and chronically stimulated T cells.Nature communications · 2026Article
- Targeting Regnase-1 in B7-H3-CAR T cells reprograms the tumor microenvironment and enhances antitumor efficacy for osteosarcoma.Cell reports. Medicine · 2026Article
- Immune niches in brain tumors: glial-immune cell interactions and spatial microdomains.Acta neuropathologica communications · 2026Review
- A Multiple Enzyme-Mimetic Platinum-Ruthenium Nanohybrid Prodrug Potentiates Chemo-/Chemodynamic-/Immuno-Therapy of Hypoxic Tumors.Advanced healthcare materials · 2026Article
- Circulating CD28Journal of translational medicine · 2026Article
- Distinct CD8iScience · 2026Article
- Multiscale predictive cellular modeling: integrating hypothesis grammars, digital twins, and multi-omics for In silico oncology and precision theranostics.Functional & integrative genomics · 2026Review
- PI3Kδ inhibition alters CD8 T cell differentiation and reprograms the tumor microenvironment following adoptive immunotherapy.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Article
- CD8+ Regulatory T Cells.Annual review of immunology · 2026Review
- Tumor immunogenicity shapes CNS immune niches and CD8⁺ T cell fate in glioblastoma.Journal of neuroinflammation · 2026Article
- Dual regulation of CXCR6Journal for immunotherapy of cancer · 2026Article
- The opportunities and barriers for developing tumour-infiltrating lymphocyte therapy for patients with advanced genitourinary cancers.Nature reviews. Urology · 2026Review
- Multimodal single-cell and spatial profiling reveals altered T cell-mediated immunity and B-cell follicular architecture in non-metastatic lymph nodes of patients with aggressive non-small cell lung cancer.medRxiv : the preprint server for health sciences · 2026Article
- Boron neutron capture therapy preserves immune cells and induces robust anti-tumour immunity in preclinical mouse model.Nature communications · 2026Article
- Glucocorticoids in breast cancer: physiologic mechanisms and relationship to risk, survival, and treatment response.Frontiers in endocrinology · 2026Review
- Rewiring tumor immunity via zinc finger proteins: a new frontier in cancer immunotherapy.Journal of translational medicine · 2025Review
217 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
19 authors at 6 institutions in 1 country.
Funding
Abstract
Reversing the dysfunctional T cell state that arises in cancer and chronic viral infections is the focus of therapeutic interventions; however, current therapies are effective in only some patients and some tumor types. To gain a deeper molecular understanding of the dysfunctional T cell state, we analyzed population and single-cell RNA profiles of CD8(+) tumor-infiltrating lymphocytes (TILs) and used genetic perturbations to identify a distinct gene module for T cell dysfunction that can be uncoupled from T cell activation. This distinct dysfunction module is downstream of intracellular metallothioneins that regulate zinc metabolism and can be identified at single-cell resolution. We further identify Gata-3, a zinc-finger transcription factor in the dysfunctional module, as a regulator of dysfunction, and we use CRISPR-Cas9 genome editing to show that it drives a dysfunctional phenotype in CD8(+) TILs. Our results open novel avenues for targeting dysfunctional T cell states while leaving activation programs intact.
Indexed as
Identifiers
What OpenQuestion holds
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.