ArticleThe Journal of experimental medicine2022
TCR signal strength defines distinct mechanisms of T cell dysfunction and cancer evasion.
Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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Who cites it
106 citing papers in PubMed, 142 citations in OpenAlex.
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- Orthogonal Chemistry Enables Precision Nanoparticle Cofunctionalization for Tuning Immune Stimulation and Antigen Presentation.Biomacromolecules · 2026Article
- The T Cell Receptor: Molecular Sensor, Therapeutic Mediator and Probabilistic Driver of Adaptive Immunity.Immunological reviews · 2026Review
- Programming the immunological properties of mRNA vaccines for cancer.Nature reviews. Immunology · 2026Review
- High-avidity TCR signaling induces a distinct KLR-positive exhaustion state in human tumor-infiltrating CD8 T cells associated with immunotherapy response.bioRxiv : the preprint server for biology · 2026Article
- Hallmarks and correlates of effective adoptive cell immunotherapy for cancer.Nature reviews. Immunology · 2026Review
- Targeting the immunological synapse in multiple myeloma.Discover oncology · 2026Review
- Analyses of single-cell and bulk RNA-sequencing datasets identify biomarker-based molecular subtypes and a prognostic signature in lung adenocarcinoma.Translational cancer research · 2026Article
- T-cell Priming by High-Avidity Neoantigens in Lymph Nodes Augments Adoptive Immunotherapy.Cancer immunology research · 2026Article
- Stepwise epigenetic signal integration drives adaptive programming of cytotoxic lymphocytes.Immunity · 2026Article
- CAR-adapted PIK3CD base editing enhances T cell anti-tumor potency.Nature cancer · 2026Article
- Regulators of CD8Nature reviews. Immunology · 2026Review
- Advancing adoptive T cell therapy in ovarian cancer: barriers, innovations, and emerging platforms.Journal for immunotherapy of cancer · 2026Review
- Article
- Tumor-driven stabilization of CD8Frontiers in immunology · 2026Review
- CAR-T cell signaling dynamics, rational design principles and artificial intelligence for next-generation chimeric antigen receptors.Frontiers in immunology · 2026Review
- Reversing T cell dysfunction in a novelFrontiers in immunology · 2026Article
- HERV-K TM Subunit Elicits CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
46 more citing papers are in PubMed but not listed here.
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22 authors at 4 institutions in 1 country.
Funding
Abstract
T cell receptor (TCR) signal strength is a key determinant of T cell responses. We developed a cancer mouse model in which tumor-specific CD8 T cells (TST cells) encounter tumor antigens with varying TCR signal strength. High-signal-strength interactions caused TST cells to up-regulate inhibitory receptors (IRs), lose effector function, and establish a dysfunction-associated molecular program. TST cells undergoing low-signal-strength interactions also up-regulated IRs, including PD1, but retained a cell-intrinsic functional state. Surprisingly, neither high- nor low-signal-strength interactions led to tumor control in vivo, revealing two distinct mechanisms by which PD1hi TST cells permit tumor escape; high signal strength drives dysfunction, while low signal strength results in functional inertness, where the signal strength is too low to mediate effective cancer cell killing by functional TST cells. CRISPR-Cas9-mediated fine-tuning of signal strength to an intermediate range improved anti-tumor activity in vivo. Our study defines the role of TCR signal strength in TST cell function, with important implications for T cell-based cancer immunotherapies.
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