ArticleClinical cancer research : an official journal of the American Association for Cancer Research2026
Preexisting TCR Clones Drive Major Pathologic Responses in Patients with HNSCC Treated with Dual Immune Checkpoint Inhibitors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2026. 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 1 paper.
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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.
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Who cites it
1 citing paper in PubMed.
- Machine Learning of Personal Repertoires From Public T Cell Receptors.Immunological reviews · 2026Review
Corrections and comments
- Erratum issued
Authors and funding
7 authors.
Funding
Abstract
purposeImmune checkpoint inhibitors (ICI) elicit variable responses in head and neck squamous cell carcinoma (HNSCC), yet mechanisms driving major pathologic responses (MPR) remain poorly defined. We sought to evaluate longitudinal CD8 T-cell repertoire evolution to identify determinants of MPR. PATIENTS AND
methodsWe analyzed high-resolution single-cell T-cell receptor (TCR) sequencing data from paired pretreatment and posttreatment CD8 tumor-infiltrating lymphocytes obtained from patients with HNSCC treated with neoadjuvant anti-PD-1 combined with either anti-CTLA-4 or anti-LAG3.
resultsContrary to the clonal replacement hypothesis, posttreatment CD8 T-cell pools were dominated by preexisting TCR clones regardless of clinical outcome. MPR was uniquely characterized by higher abundance and greater expansion magnitude of super-expanded clones. We developed the TCR adaptivity index (TAI) to quantify coordinate flux (expansion and contraction) of all TCR clones detected across pretreatment and posttreatment time points; this index emerged as the most significant parameter associated with MPR. Importantly, clonal expansion in non-MPR was uncoupled from the productive, therapy-induced transcriptional reprogramming-characterized by markers of effector vigor and cellular fitness-that was observed in MPR. Furthermore, expansion dynamics positively correlated with predicted tumor reactivity as calculated by the tumor-reactive signature (TRS) score. Finally, a TRS-integrated TAI remained significantly correlated with MPR.
conclusionsDual-ICI drives MPR predominantly through the adaptivity and functional reprogramming of preexisting immunity. Successful therapy relies on a coordinate repertoire response that promotes transition of putative tumor-reactive super-expanders into productive functional states. TRS-integrated TAI provides a high-throughput framework incorporating clonal dynamics and functional reprogramming to predict therapeutic efficacy.
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