scholarly journals 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

2022 ◽  
Vol 12 ◽  
Author(s):  
Yi-Tung Chen ◽  
Hung-Chih Hsu ◽  
Yun-Shien Lee ◽  
Hsuan Liu ◽  
Bertrand Chin-Ming Tan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cell Receptor ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Dynamic Change ◽  
Cell Receptor ◽  
Healthy Controls ◽  
Tcr Repertoire ◽  
Tcr Diversity ◽  
Treatment Responses

Colorectal cancer (CRC) is a major cause of cancer mortality and morbidity. Despite advances in chemotherapy and targeted therapy, unsustainable clinical benefit was noted due to recurrence and therapy resistance. The immune status of the cancer patient may affect the effectiveness of disease treatments. The dynamic change in the T-cell receptor (TCR) repertoire might be a clinical parameter for monitoring treatment responses. In this study, we aimed to determine the characteristics and clinical significance of the TCR repertoire in patients with unresectable metastatic colorectal cancer (mCRC). Herein, we comprehensively profile 103 peripheral blood samples from 20 healthy controls and 16 CRC patients with a follow-up of 98 to 452 days to identify hypervariable rearrangements of the TCRα and TCRβ repertoires using high-throughput sequencing. We found that TCRα repertoires, TCRβ repertoires, and CDR3 clonotypes were altered in mCRC patients compared with healthy controls. The diversity of TCR repertoires and CDR3 clonotypes decreased in most mCRC patients after therapy. Furthermore, compared with baseline TCR diversity, patients whose TCR diversity dropped considerably during therapy had better treatment responses, including lower CEA and CA19-9 levels and smaller tumor sizes. TCR baseline diversity was also significantly associated with partial response (PR) status (odds ratio: 5.29, p = 0.04). In conclusion, the present study demonstrated the association between dynamic changes in TCR diversity during chemotherapy and clinical outcomes as well as the potential utility of the TCR repertoire in predicting the prognosis of cancer treatment.

scholarly journals Genesis of the αβ T-cell receptor

2018 ◽  
Author(s):  
Thomas Dupic ◽  
Quentin Marcou ◽  
Aleksandra M. Walczak ◽  
Thierry Mora
Keyword(s):  
Statistical Analysis ◽  
T Cell ◽  
T Cell Receptor ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Mechanistic Model ◽  
Cell Receptor ◽  
Generation Process ◽  
Generative Process ◽  
Tcr Repertoire

The T-cell (TCR) repertoire relies on the diversity of receptors composed of two chains, called α and β, to recognize pathogens. Using results of high throughput sequencing and computational chain-pairing experiments of human TCR repertoires, we quantitively characterize the αβ generation process. We estimate the probabilities of a rescue recombination of the β chain on the second chromosome upon failure or success on the first chromosome. Unlike β chains, α chains recombine simultaneously on both chromosomes, resulting in correlated statistics of the two genes which we predict using a mechanistic model. We find that ∼28% of cells express both α chains. Altogether, our statistical analysis gives a complete quantitative mechanistic picture that results in the observed correlations in the generative process. We learn that the probability to generate any TCRαβ is lower than 10–12 and estimate the generation diversity and sharing properties of the αβ TCR repertoire.

scholarly journals Research Techniques Made Simple: High-Throughput Sequencing of the T-Cell Receptor

2017 ◽  
Vol 137 (6) ◽  
pp. e131-e138 ◽  
Author(s):  
Tiago R. Matos ◽  
Menno A. de Rie ◽  
Marcel B.M. Teunissen
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Cell Receptor ◽  
Research Techniques

scholarly journals TCRdb: a comprehensive database for T-cell receptor sequences with powerful search function

2020 ◽  
Vol 49 (D1) ◽  
pp. D468-D474 ◽  
Author(s):  
Si-Yi Chen ◽  
Tao Yue ◽  
Qian Lei ◽  
An-Yuan Guo
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Length Distribution ◽  
Cell Types ◽  
Cell Receptor ◽  
Search Function ◽  
Tcr Repertoire ◽  
Tcr Diversity ◽  
Clinical Conditions ◽  
T Cell Immunology

Abstract T cells and the T-cell receptor (TCR) repertoire play pivotal roles in immune response and immunotherapy. TCR sequencing (TCR-Seq) technology has enabled accurate profiling TCR repertoire and currently a large number of TCR-Seq data are available in public. Based on the urgent need to effectively re-use these data, we developed TCRdb, a comprehensive human TCR sequences database, by a uniform pipeline to characterize TCR sequences on TCR-Seq data. TCRdb contains more than 277 million highly reliable TCR sequences from over 8265 TCR-Seq samples across hundreds of tissues/clinical conditions/cell types. The unique features of TCRdb include: (i) comprehensive and reliable sequences for TCR repertoire in different samples generated by a strict and uniform pipeline of TCRdb; (ii) powerful search function, allowing users to identify their interested TCR sequences in different conditions; (iii) categorized sample metadata, enabling comparison of TCRs in different sample types; (iv) interactive data visualization charts, describing the TCR repertoire in TCR diversity, length distribution and V-J gene utilization. The TCRdb database is freely available at http://bioinfo.life.hust.edu.cn/TCRdb/ and will be a useful resource in the research and application community of T cell immunology.

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