ArticleProceedings of the National Academy of Sciences of the United States of America2013
T-cell receptor affinity and avidity defines antitumor response and autoimmunity in T-cell immunotherapy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 167 papers.
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
167 citing papers in PubMed, 240 citations in OpenAlex.
- Fine-tuning affinity and spacer design enhances T cell potency in DLL3 and BCMA CAR T cells.mAbs · 2026Article
- Article
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- α2,6-Sialoglycan-regulated antitumor immunity of tumor-infiltrating CD8Nature chemical biology · 2026Article
- TcrDesign: de novo design of epitope-specific full-length T cell receptors.Science China. Life sciences · 2026Article
- Heterogeneity and dynamics of DENV-specific CD8 + T cells in dengue infection.Nature communications · 2026Article
- Hallmarks and correlates of effective adoptive cell immunotherapy for cancer.Nature reviews. Immunology · 2026Review
- SwiftTCR: efficient computational docking protocol of TCRpMHC-I complexes using restricted rotation matrices.Briefings in bioinformatics · 2026Article
- T-cell Priming by High-Avidity Neoantigens in Lymph Nodes Augments Adoptive Immunotherapy.Cancer immunology research · 2026Article
- Article
- CD2 costimulation strength: A key regulator of T cell function and anti-tumor immunity that is epigenetically regulated.iScience · 2025Article
- A kinetic gatekeeper: TCR-pMHC dissociation dynamics determine T cell activation efficacy.Protein science : a publication of the Protein Society · 2025Article
- T cell receptor specificity landscape revealed through de novo peptide design.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Design of a potent interleukin-21 mimic for cancer immunotherapy.Science immunology · 2025Article
- Article
- T-cell receptor specificity landscape revealed through de novo peptide design.bioRxiv : the preprint server for biology · 2025Article
- Deciphering Depigmentation: Mouse Models for Vitiligo Research.The Journal of investigative dermatology · 2025Review
- TCR-T Cell Recognition of an NY-ESO-1 Epitope Presented by HLA-A2 Supertype: Implications for Cancer Immunotherapy.Vaccines · 2025Article
- Development of an innovative approach for early diagnosis of cervical cancer using TCR‑like antibodies targeting HPV18 E6 and E7 peptides.Molecular medicine reports · 2025Article
- A pan-cancer atlas of therapeutic T cell targets.bioRxiv : the preprint server for biology · 2025Article
107 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
T cells expressing antigen-specific T-cell receptors (TCRs) can mediate effective tumor regression, but they often also are accompanied by autoimmune responses. To determine the TCR affinity threshold defining the optimal balance between effective antitumor activity and autoimmunity in vivo, we used a unique self-antigen system comprising seven human melanoma gp100(209-217)-specific TCRs spanning physiological affinities (1-100 μM). We found that in vitro and in vivo T-cell responses are determined by TCR affinity, except in one case that was compensated by substantial CD8 involvement. Strikingly, we found that T-cell antitumor activity and autoimmunity are closely coupled but plateau at a defined TCR affinity of 10 µM, likely due to diminished contribution of TCR affinity to avidity above the threshold. Together, these results suggest that a relatively low-affinity threshold is necessary for the immune system to avoid self-damage, given the close relationship between antitumor activity and autoimmunity. The low threshold, in turn, indicates that adoptive T-cell therapy treatment strategies using in vitro-generated high-affinity TCRs do not necessarily improve efficacy.
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.