Single-Cell TCR and Transcriptome Analysis: An Indispensable Tool for Studying T-Cell Biology and Cancer Immunotherapy

Pasetto, Anna; Lu, Yong

doi:10.3389/fimmu.2021.689091

Cited by 19 publications

(15 citation statements)

References 125 publications

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“…Current high-throughput sequencing techniques that use genomic DNA (gDNA) or RNA as starting materials to construct a TCR repertoire have advantages and limitations, and the optimal choice depends on the study of interest ( Figure 2A ). Approaches based on gDNA employ multiplex amplification, a set of forward PCR primers complementary to all possible V segments and a set of reverse primers complementary to the J segments ( 98 , 99 ). gDNA is stable, and there is only one copy of single gDNA in each cell to encode TCR.…”

Section: High-throughput Technology Revolutionized Methods For Measuring Alloresponsementioning

confidence: 99%

Analysis of T-Cell Receptor Repertoire in Transplantation: Fingerprint of T Cell-mediated Alloresponse

Tian

2022

Front. Immunol.

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T cells play a key role in determining allograft function by mediating allogeneic immune responses to cause rejection, and recent work pointed their role in mediating tolerance in transplantation. The unique T-cell receptor (TCR) expressed on the surface of each T cell determines the antigen specificity of the cell and can be the specific fingerprint for identifying and monitoring. Next-generation sequencing (NGS) techniques provide powerful tools for deep and high-throughput TCR profiling, and facilitate to depict the entire T cell repertoire profile and trace antigen-specific T cells in circulation and local tissues. Tailing T cell transcriptomes and TCR sequences at the single cell level provides a full landscape of alloreactive T-cell clones development and biofunction in alloresponse. Here, we review the recent advances in TCR sequencing techniques and computational tools, as well as the recent discovery in overall TCR profile and antigen-specific T cells tracking in transplantation. We further discuss the challenges and potential of using TCR sequencing-based assays to profile alloreactive TCR repertoire as the fingerprint for immune monitoring and prediction of rejection and tolerance.

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Section: High-throughput Technology Revolutionized Methods For Measuring Alloresponsementioning

confidence: 99%

Analysis of T-Cell Receptor Repertoire in Transplantation: Fingerprint of T Cell-mediated Alloresponse

Tian

2022

Front. Immunol.

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“…This allows to identify whether certain sequences were originally present at high abundance—identical sequences with different UMIs—or the same sequence is highly abundant because it was preferentially amplified by the PCR—equal sequences with the same UMI. Recent advances in TCR repertoire analysis now allow to combine single-cell TCR sequencing with transcriptomics analysis [ 24 , 25 , 26 , 27 ]. This has been specially interesting to link signatures of tumour-reactive T cells with their TCRs, although usually the aim of using these technologies is not to analyse diversity but to describe tumour-specific TCRs [ 28 ].…”

Section: T Cell Receptormentioning

confidence: 99%

“…Even further improved, spatial transcriptomics, developed by Stahl PL et al [ 29 ], now allows to perform a transcriptomic analysis in situ, with the aim to retain the cellular location information. There are still few cancer studies in which the TCR analysis and spatial transcriptomics are combined [ 26 , 30 , 31 , 32 ], but it will likely be increasingly used in the future.…”

Section: T Cell Receptormentioning

confidence: 99%

Evaluation of the TCR Repertoire as a Predictive and Prognostic Biomarker in Cancer: Diversity or Clonality?

Aran

Garrigós²,

Curigliano

et al. 2022

Cancers

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T cells play a vital role in the anti-tumoural response, and the presence of tumour-infiltrating lymphocytes has shown to be directly correlated with a good prognosis in several cancer types. Nevertheless, some patients presenting tumour-infiltrating lymphocytes do not have favourable outcomes. The TCR determines the specificities of T cells, so the analysis of the TCR repertoire has been recently considered to be a potential biomarker for patients’ progression and response to therapies with immune checkpoint inhibitors. The TCR repertoire is one of the multiple elements comprising the immune system and is conditioned by several factors, including tissue type, tumour mutational burden, and patients’ immunogenetics. Its study is crucial to understanding the anti-tumoural response, how to beneficially modulate the immune response with current or new treatments, and how to better predict the prognosis. Here, we present a critical review including essential studies on TCR repertoire conducted in patients with cancer with the aim to draw the current conclusions and try to elucidate whether it is better to encounter higher clonality with few TCRs at higher frequencies, or higher diversity with many different TCRs at lower frequencies.

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“…Cancer is derived from a series of genetic alterations that occur in normal cells that are transformed into malignant cells [ 141 ], capable of invading the surrounding normal tissue and generating metastasis.…”

Section: Tcr and Cancermentioning

confidence: 99%

T-Cell Receptor Repertoire Sequencing and Its Applications: Focus on Infectious Diseases and Cancer

Mazzotti

Gaimari

Bravaccini

et al. 2022

IJMS

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The immune system is a dynamic feature of each individual and a footprint of our unique internal and external exposures. Indeed, the type and level of exposure to physical and biological agents shape the development and behavior of this complex and diffuse system. Many pathological conditions depend on how our immune system responds or does not respond to a pathogen or a disease or on how the regulation of immunity is altered by the disease itself. T-cells are important players in adaptive immunity and, together with B-cells, define specificity and monitor the internal and external signals that our organism perceives through its specific receptors, TCRs and BCRs, respectively. Today, high-throughput sequencing (HTS) applied to the TCR repertoire has opened a window of opportunity to disclose T-cell repertoire development and behavior down to the clonal level. Although TCR repertoire sequencing is easily accessible today, it is important to deeply understand the available technologies for choosing the best fit for the specific experimental needs and questions. Here, we provide an updated overview of TCR repertoire sequencing strategies, providers and applications to infectious diseases and cancer to guide researchers’ choice through the multitude of available options. The possibility of extending the TCR repertoire to HLA characterization will be of pivotal importance in the near future to understand how specific HLA genes shape T-cell responses in different pathological contexts and will add a level of comprehension that was unthinkable just a few years ago.

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Single-Cell TCR and Transcriptome Analysis: An Indispensable Tool for Studying T-Cell Biology and Cancer Immunotherapy

Cited by 19 publications

References 125 publications

Analysis of T-Cell Receptor Repertoire in Transplantation: Fingerprint of T Cell-mediated Alloresponse

Analysis of T-Cell Receptor Repertoire in Transplantation: Fingerprint of T Cell-mediated Alloresponse

Evaluation of the TCR Repertoire as a Predictive and Prognostic Biomarker in Cancer: Diversity or Clonality?

T-Cell Receptor Repertoire Sequencing and Its Applications: Focus on Infectious Diseases and Cancer

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