T Cell Receptor Beta-Chain Profiling of Tumor Tissue, Peripheral Blood and Regional Lymph Nodes From Patients With Papillary Thyroid Carcinoma

Wang, Yizeng; Liu, Yuanchao; Chen, Li; Chen, Zuoyu; Wang, Xiaoning; Jiang, Ruoyu; Zhao, Ke; He, Xianghui

doi:10.3389/fimmu.2021.595355

Cited by 9 publications

(8 citation statements)

References 32 publications

(24 reference statements)

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“…Without injury, CD44 high Tregs were found to have higher TCRα/TCRβ clonality than CD44 low Tregs as determined lower D50 and diversity index (Di) values ( Figure 3B ). The D50 value indicates the percentage of TCR CDR3 sequences that account for 50% of the total unique CDR3 sequence reads, so low D50 values would indicate high clonality ( 41 , 42 ). Interestingly, the D50 value decreased for TCRα in CD44 high Tregs (uninjured = 9.7, injured = 5.5), but D50 for TCRβ did not change following injury suggesting that TCRα clonality is influence by injury.…”

Section: Resultsmentioning

confidence: 99%

Distinct Injury Responsive Regulatory T Cells Identified by Multi-Dimensional Phenotyping

et al. 2022

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CD4+ regulatory T cells (Tregs) activate and expand in response to different types of injuries, suggesting that they play a critical role in controlling the immune response to tissue and cell damage. This project used multi-dimensional profiling techniques to comprehensively characterize injury responsive Tregs in mice. We show that CD44high Tregs expand in response to injury and were highly suppressive when compared to CD44low Tregs. T cell receptor (TCR) repertoire analysis revealed that the CD44high Treg population undergo TCRαβ clonal expansion as well as increased TCR CDR3 diversity. Bulk RNA sequencing and single-cell RNA sequencing with paired TCR clonotype analysis identified unique differences between CD44high and CD44low Tregs and specific upregulation of genes in Tregs with expanded TCR clonotypes. Gene ontology analysis for molecular function of RNA sequencing data identified chemokine receptors and cell division as the most enriched functional terms in CD44high Tregs versus CD44low Tregs. Mass cytometry (CyTOF) analysis of Tregs from injured and uninjured mice verified protein expression of these genes on CD44high Tregs, with injury-induced increases in Helios, Galectin-3 and PYCARD expression. Taken together, these data indicate that injury triggers the expansion of a highly suppressive CD44high Treg population that is transcriptionally and phenotypically distinct from CD44low Tregs suggesting that they actively participate in controlling immune responses to injury and tissue damage.

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Section: Resultsmentioning

confidence: 99%

Distinct Injury Responsive Regulatory T Cells Identified by Multi-Dimensional Phenotyping

et al. 2022

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“…Although the amounts of TILs in PTC-W and PTC-WO have been investigated, TCR repertoire analysis of TILs was seldom been reported (21,22). To our knowledge, we firstly investigated the spatial heterogeneity of the TCR repertoire in PTC with and without existing HT as well as the relationship of the TCR repertoire between PTC with and without existing HT, which will contribute to practical applications for personalized treatment.…”

Section: Discussionmentioning

confidence: 99%

Clonal Distribution and Intratumor Heterogeneity of the TCR Repertoire in Papillary Thyroid Cancer With or Without Coexistent Hashimoto’s Thyroiditis

Cui

Zhang²,

Ding³

et al. 2022

Front. Immunol.

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The intratumor heterogeneity (ITH) of the amount and TCR repertoires of tumor infiltrating lymphocytes (TILs) in PTC with and without coexistent Hashimoto’s thyroiditis (HT) are unclear. Here, we investigated the amount of T cells in tumor and corresponding normal tissues by immunohistochemical staining on 80 tumor samples and 40 normal samples from 40 patients. The immune repertoire of T cells was identified on 24 tumor samples and 12 normal samples from 12 patients using TCR high-throughput sequencing. The results demonstrated that the numbers of CD3+, CD4+ and CD8+ T cells in PTC without coexistent HT (PTC-WO) were significantly lower than those in PTC with existing HT (PTC-W). In PTC-W, the density of CD4+ TILs were generally higher when compared with CD8+ TILs. Furthermore, we found that the numbers of CD3+ T cells and their CD4+, CD8+ subtypes in tumor samples were generally higher than those in normal tissue in PTC-WO and moreover, the number of CD3+ T cells was negatively associated with TCR clonality in PTC-WO. In addition, although ITH of the TCR repertoire truly existed in PTC-W and PTC-WO, the TCR repertoires between distinct regions of the non-adjacent tumor foci were presented with a higher degree of similarity than those between tumor and matched normal tissue in PTC-WO, yet the similarity of intratumor repertoires was not significantly higher than those between tumor and corresponding normal samples in PTC-W. This research comprehensively delineated the quantity and TCR repertoire ITH of T cells in PTC-W and PTC-WO, suggesting that TILs might be reactive to tumor antigens in PTC-WO. Moreover, multiregion biopsies should be performed to precisely identify the immune background in PTC-W and PTC-WO.

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“…The purified libraries were analyzed by Agilent 2100 Bioanalyzer to determine the length and quantity. The samples with approximately 10 nM DNA and sequenced with the Illumina NovaSeq system with PE150 mode [45].…”

Section: Methodsmentioning

confidence: 99%

Comprehensive analysis of T‐cell receptor repertoires reveals antigen‐driven T‐cell clusters in patients with Behçet's syndrome

Zou

et al. 2023

Eur J Immunol

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T lymphocytes are the major components of adaptive immunity in Behçet's syndrome (BS) pathology. However, the precise mechanism of T‐cell‐induced inflammatory condition remains to be determined. We applied bulk sequencing of the T‐cell receptor (TCR) β chain in peripheral blood samples from 45 patients with BS and 10 healthy donors as controls. TCR repertoires in BS patients displayed more clonality and less diversity than in healthy donors. Male patients exhibited lower diversity metrics of TCR and had a larger proportion in the top 10 clones than females (p = 0.016). There were no TCR clonality differences in other clinical features, such as age, disease duration, organ involvement, disease severity, and activity. By “Grouping of Lymphocyte Interactions by Paratope Hotspots” (GLIPH2) for antigen prediction, we found distinct 2477 clusters of TCR‐β sequences that potentially recognize similar antigens shared between BS patients. We observed clonal T‐cell expansion in BS patients. Sexual differences in TCR clonal expansion and public TCR groups deserve further study to reveal the underline T‐cell‐mediated immunity in BS.

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T Cell Receptor Beta-Chain Profiling of Tumor Tissue, Peripheral Blood and Regional Lymph Nodes From Patients With Papillary Thyroid Carcinoma

Cited by 9 publications

References 32 publications

Distinct Injury Responsive Regulatory T Cells Identified by Multi-Dimensional Phenotyping

Distinct Injury Responsive Regulatory T Cells Identified by Multi-Dimensional Phenotyping

Clonal Distribution and Intratumor Heterogeneity of the TCR Repertoire in Papillary Thyroid Cancer With or Without Coexistent Hashimoto’s Thyroiditis

Comprehensive analysis of T‐cell receptor repertoires reveals antigen‐driven T‐cell clusters in patients with Behçet's syndrome

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