ArticleOncotarget2017
Multi-omics study revealing the complexity and spatial heterogeneity of tumor-infiltrating lymphocytes in primary liver carcinoma.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 47 citations in OpenAlex.
- Landscape of T-cell exhaustion heterogeneity and HBV integration in virus-related HCC revealed by whole-exome, transcriptome, and single-cell sequencing.JHEP reports : innovation in hepatology · 2025Article
- Spatial heterogeneity reveals an evolutionary signature predicting therapeutic response and clinical outcomes in hepatocellular carcinoma.Frontiers in bioinformatics · 2025Article
- Comparative transcriptomic and genomic analysis of tumor cells in the marginal and center regions of tumor nests in human hepatocellular carcinoma.Frontiers in cell and developmental biology · 2025Article
- Immune characteristics of dedifferentiated retroperitoneal liposarcomas and the reliability of regional samples in evaluating their tumor immune microenvironments.World journal of surgical oncology · 2024Article
- Globally shared TCR repertoires within the tumor-infiltrating lymphocytes of patients with metastatic gynecologic cancer.Scientific reports · 2023Article
- A transcriptomic intratumour heterogeneity-free signature overcomes sampling bias in prognostic risk classification for hepatocellular carcinoma.JHEP reports : innovation in hepatology · 2023Article
- Prognostic value of various immune cells and Immunoscore in triple-negative breast cancer.Frontiers in immunology · 2023Article
- Multi-region sequencing with spatial information enables accurate heterogeneity estimation and risk stratification in liver cancer.Genome medicine · 2022Article
- Advances in single-cell sequencing technology in the field of hepatocellular carcinoma.Frontiers in genetics · 2022Review
- Article
- Tumour evolution in hepatocellular carcinoma.Nature reviews. Gastroenterology & hepatology · 2020Review
- A four-factor immune risk score signature predicts the clinical outcome of patients with spinal chordoma.Clinical and translational medicine · 2020Article
- Fully moderated t-statistic in linear modeling of mixed effects for differential expression analysis.BMC bioinformatics · 2019Article
- The adequacy of tissue microarrays in the assessment of inter- and intra-tumoural heterogeneity of infiltrating lymphocyte burden in leiomyosarcoma.Scientific reports · 2019Article
- Comprehensive immune characterization and T-cell receptor repertoire heterogeneity of retroperitoneal liposarcoma.Cancer science · 2019Article
- Review
- Characterization of Distinct T Cell Receptor Repertoires in Tumor and Distant Non-tumor Tissues from Lung Cancer Patients.Genomics, proteomics & bioinformatics · 2019Article
- Genome sequencing as a first-line genetic test in familial dilated cardiomyopathy.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Article
- T cell receptor repertoire profiling predicts the prognosis of HBV-associated hepatocellular carcinoma.Cancer medicine · 2018Article
- Antigen Identification for Orphan T Cell Receptors Expressed on Tumor-Infiltrating Lymphocytes.Cell · 2018Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intratumoral heterogeneity has been revealed in primary liver carcinoma (PLC). However, spatial heterogeneity of tumor-infiltrating lymphocytes (TILs), which reflects one dimension of a tumor's spatial heterogeneity, and the relationship between TIL diversity, local immune response and mutation burden remain unexplored in PLC. Therefore, we performed immune repertoire sequencing, gene expression profiling analysis and whole-exome sequencing in parallel on five regions of each tumor and on matched adjacent normal tissues and peripheral blood from five PLC patients. A significantly higher cumulative frequency of the top 250 most abundant TIL clones was observed in tumors than in peripheral blood. Besides, overlap rates of T cell receptor (TCR) repertoire for intratumor comparisons, significant higher than those for tumor-adjacent normal tissue comparisons and tumor-blood comparisons, which provide evidence for antigen-driven clonal expansion in PLC. Analysis of the percentage of ubiquitous TCR sequences, regional frequencies of each clone and TIL diversity suggested TIL clones varying between distinct regions of the same tumor, which indicated weak TCR repertoire similarity within a single tumor. Furthermore, correlation analysis revealed that TIL diversity significantly correlated with the expression of immune response genes rather than the mutation load. We conclude that intratumoural T-cell clones are spatially heterogeneous, which can lead to underestimate the immune profile of PLC from a single biopsy sample and may present challenge to adoptive cell therapy using autologous TILs. TIL diversity provides a reasonable explanation for the degree of immune response, implied TIL diversity can serve as a surrogate marker to monitor the effect of immunotherapy.
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