ArticleThe Journal of pathology2013
Ultra-deep T cell receptor sequencing reveals the complexity and intratumour heterogeneity of T cell clones in renal cell carcinomas.
Article in The Journal of pathology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 106 citations in OpenAlex.
- High Response Rate and Durability Driven by HLA Genetic Diversity in Patients with Kidney Cancer Treated with Lenvatinib and Pembrolizumab.Molecular cancer research : MCR · 2021Trial
- T cell immunomonitoring: a comparative analysis of traditional and novel methods to quantify and characterize human antigen-specific T cells.Nature protocols · 2026Review
- Charting intratumor heterogeneity from bench to bedside.Nature cancer · 2026Review
- T-Cell Receptor Repertoires Show Dynamic Variation Between Diagnosis and Relapse of Diffuse Large B-Cell Lymphoma.EJHaem · 2025Article
- Pomalidomide in patients with multiple myeloma: potential impact on the reconstitution of a functional T-cell immunity.Immunologic research · 2024Article
- Human TCR repertoire in cancer.Cancer medicine · 2024Review
- Fatty acids metabolism affects the therapeutic effect of anti-PD-1/PD-L1 in tumor immune microenvironment in clear cell renal cell carcinoma.Journal of translational medicine · 2023Article
- T-Cell Receptor Repertoire Sequencing in the Era of Cancer Immunotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- T-cell repertoire diversity: friend or foe for protective antitumor response?Journal of experimental & clinical cancer research : CR · 2022Review
- Heterogeneity and evolution of tumour immune microenvironment in metastatic gastroesophageal adenocarcinoma.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2022Article
- Impact of cancer evolution on immune surveillance and checkpoint inhibitor response.Seminars in cancer biology · 2022Review
- Intratumor heterogeneity: the hidden barrier to immunotherapy against MSI tumors from the perspective of IFN-γ signaling and tumor-infiltrating lymphocytes.Journal of hematology & oncology · 2021Review
- Autoencoder based local T cell repertoire density can be used to classify samples and T cell receptors.PLoS computational biology · 2021Article
- CDR3 and V genes show distinct reconstitution patterns in T cell repertoire post-allogeneic bone marrow transplantation.Immunogenetics · 2021Article
- DeepTCR is a deep learning framework for revealing sequence concepts within T-cell repertoires.Nature communications · 2021Article
- Distinct T cell receptor repertoire diversity of clinically defined high-grade serous ovarian cancer treatment subgroups.iScience · 2021Article
- Longitudinal High-Throughput Sequencing of the T-Cell Receptor Repertoire Reveals Dynamic Change and Prognostic Significance of Peripheral Blood TCR Diversity in Metastatic Colorectal Cancer During Chemotherapy.Frontiers in immunology · 2021Article
- Characteristics of T-Cell Receptor Repertoire and Correlation WithFrontiers in oncology · 2021Article
- Characteristics, dynamic changes, and prognostic significance of TCR repertoire profiling in patients with renal cell carcinoma.The Journal of pathology · 2020Article
- Spatially resolved analyses link genomic and immune diversity and reveal unfavorable neutrophil activation in melanoma.Nature communications · 2020Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 7 institutions in 2 countries.
Funding
Abstract
The recognition of cancer cells by T cells can impact upon prognosis and be exploited for immunotherapeutic approaches. This recognition depends on the specific interaction between antigens displayed on the surface of cancer cells and the T cell receptor (TCR), which is generated by somatic rearrangements of TCR α- and β-chains (TCRb). Our aim was to assess whether ultra-deep sequencing of the rearranged TCRb in DNA extracted from unfractionated clear cell renal cell carcinoma (ccRCC) samples can provide insights into the clonality and heterogeneity of intratumoural T cells in ccRCCs, a tumour type that can display extensive genetic intratumour heterogeneity (ITH). For this purpose, DNA was extracted from two to four tumour regions from each of four primary ccRCCs and was analysed by ultra-deep TCR sequencing. In parallel, tumour infiltration by CD4, CD8 and Foxp3 regulatory T cells was evaluated by immunohistochemistry and correlated with TCR-sequencing data. A polyclonal T cell repertoire with 367-16 289 (median 2394) unique TCRb sequences was identified per tumour region. The frequencies of the 100 most abundant T cell clones/tumour were poorly correlated between most regions (Pearson correlation coefficient, -0.218 to 0.465). 3-93% of these T cell clones were not detectable across all regions. Thus, the clonal composition of T cell populations can be heterogeneous across different regions of the same ccRCC. T cell ITH was higher in tumours pretreated with an mTOR inhibitor, which could suggest that therapy can influence adaptive tumour immunity. These data show that ultra-deep TCR-sequencing technology can be applied directly to DNA extracted from unfractionated tumour samples, allowing novel insights into the clonality of T cell populations in cancers. These were polyclonal and displayed ITH in ccRCC. TCRb sequencing may shed light on mechanisms of cancer immunity and the efficacy of immunotherapy approaches.
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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.