Evaluation and comparison of adaptive immunity through analyzing the diversities and clonalities of T-cell receptor repertoires in the peripheral blood

Zhuo, Yue; Yang, Xin; Peng, Shuai; Yang, Linjun; Wen, Xueping; Zhong, Xuemei; Yang, Shihan; Xu, Sheng; Liu, Yuping; Zhang, Zhixin

doi:10.3389/fimmu.2022.916430

Cited by 11 publications

(8 citation statements)

References 47 publications

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“…Interestingly, the middle 3 amino acids of the private CDR3 motifs contain significantly higher portion of hydrophobic residues than those of the public motifs, and hydrophobicity has been described as a hallmark of immunogenic neo-epitopes, suggesting that private CDR3 sequences might have higher potential for tumor-Ag recognition [ 69 , 70 ]. Finally, as emerging from recent findings by Zhuo et al, healthy elder individuals similarly to cancer patients, display a very poor TCR diversity within the periphery, revealing alteration of TCR repertoire in aging and oncogenesis, suggesting a possible use of circulating TCR profiling as marker of immune cell fitness in clinical practice [ 71 ].…”

Section: Introductionmentioning

confidence: 99%

T-cell repertoire diversity: friend or foe for protective antitumor response?

Porciello¹,

Franzese

D’Ambrosio³

et al. 2022

J Exp Clin Cancer Res

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Profiling the T-Cell Receptor (TCR) repertoire is establishing as a potent approach to investigate autologous and treatment-induced antitumor immune response. Technical and computational breakthroughs, including high throughput next-generation sequencing (NGS) approaches and spatial transcriptomics, are providing unprecedented insight into the mechanisms underlying antitumor immunity. A precise spatiotemporal variation of T-cell repertoire, which dynamically mirrors the functional state of the evolving host-cancer interaction, allows the tracking of the T-cell populations at play, and may identify the key cells responsible for tumor eradication, the evaluation of minimal residual disease and the identification of biomarkers of response to immunotherapy. In this review we will discuss the relationship between global metrics characterizing the TCR repertoire such as T-cell clonality and diversity and the resultant functional responses. In particular, we will explore how specific TCR repertoires in cancer patients can be predictive of prognosis or response to therapy and in particular how a given TCR re-arrangement, following immunotherapy, can predict a specific clinical outcome. Finally, we will examine current improvements in terms of T-cell sequencing, discussing advantages and challenges of current methodologies.

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Section: Introductionmentioning

confidence: 99%

T-cell repertoire diversity: friend or foe for protective antitumor response?

Porciello¹,

Franzese

D’Ambrosio³

et al. 2022

J Exp Clin Cancer Res

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“…High-throughput sequencing of TCRβ genes was performed using previously described methods [29] . In brief, we extracted total genome DNA from peripheral blood.…”

Section: Methodsmentioning

confidence: 99%

“…Better diversity corresponds to higher D50, Shannon and Simpson indices, and lower frequency of the largest clone. D50 is defined as the ratio of the numbers TCR clones that account of half of the total TCR sequences in one sample [29] . The formulas of Shannon index and Simpson index were as follows (i.e., eq.…”

Section: Methodsmentioning

confidence: 99%

A clinical-information-free method for early diagnosis of lung cancer from the patients with pulmonary nodules based on backpropagation neural network model

Yang,

Wu,

Liu

et al. 2024

Computational and Structural Biotechnology Journal

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“…Following the protocol we previously published ( Zhuo et al., 2022 ), TCRβ variable region genes were amplified through RT-PCR using RNA extracted from peripheral blood mononuclear cells (PBMCs) as a template without previous T cell subsets isolation, and then sequenced.…”

Section: Methodsmentioning

confidence: 99%

T cell receptor repertoire as a novel indicator for identification and immune surveillance of patients with severe obstructive sleep apnea

Zhuo

et al. 2023

PeerJ

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Background Obstructive sleep apnea (OSA) is the most prevalent sleep disturbance that affects approximately 936 million people worldwide and leads to extensively increased incidence of cardiovascular disease, metabolic syndrome, neurological disorders, and traffic accidents. Severe OSA patients suffer a significantly higher risk of complications and worse comorbidity outcomes. Notwithstanding, with inadequate access to contact diagnosis based on polysomnography (PSG), numerous patients with severe sleep apnea have not been diagnosed, especially during the pandemic. Moreover, how the T cell immunity is impaired in OSA remains largely unknown. Methods We primarily investigated the T cell receptor (TCR) repertoires of 50 patients with severe OSA, 23 patients with mild-to-moderate OSA, 23 patients without OSA, and 157 healthy individuals, from their peripheral blood. Firstly, we compared the clinical characteristics, blood cell counts, the ratio of neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and CD4+/CD8+T cell count between groups. Then, we compared the diversity, clonotypes, unique VJ alleles in patients with different disease severity. Furthermore, by identifying a series of disease-associated amino acid sequences, we employed a repeated hold-out machine learning strategy to explore the optimal algorithm for calculating the TCR repertoire characteristic Index (OSA-TCI). We further confirmed its relation with clinical features by linear regression analysis. Moreover, in followup of severe OSA patients who accepted adherent non-invasive ventilation, we assessed the changes of TCR repertoires, OSA-TCI, ESS, NLR, PLR, and CD4+/CD8+T after therapy. Results We found an unexpected increase in diversity and clonotypes in the TCR repertoire of OSA patients. Furthermore, we successfully developed a novel indicator termed OSA-TCI to summarize the unique repertoire alteration, which provided 90% of sensitivity and 87% of specificity in distinguishing severe OSA. In rationalization, OSA-TCI was found correlated to AHI, BMI, hemoglobin, N1, N2 percentage of sleep, snoring, smoking and lowest oxygen saturation, but only independently related to AHI (R = 0.603) and smoking (R = 0.22). Finally, we observed OSA-TCI in the eight severe patients decreased significantly after home noninvasive ventilation for three months during follow-up, consistently in line with the TCR repertoire improvement. In contrast, NLR, PLR, and the ratio of CD4+/CD8+T cell count were found useless to diagnose and therapeutic surveillance of severe OSA. Conclusions Our study is the first to unveil the TCR repertoire alteration in OSA, indicates possible insidious autoimmune mechanisms underlying OSA, and suggests that TCR repertoires serve as a convenient peripheral blood biomarker for OSA assessment without long-time contact and facility/instrument occupation. It may shed light on future diagnostic, immunological, pathophysiological, and prognostic research on OSA.

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Evaluation and comparison of adaptive immunity through analyzing the diversities and clonalities of T-cell receptor repertoires in the peripheral blood

Cited by 11 publications

References 47 publications

T-cell repertoire diversity: friend or foe for protective antitumor response?

T-cell repertoire diversity: friend or foe for protective antitumor response?

A clinical-information-free method for early diagnosis of lung cancer from the patients with pulmonary nodules based on backpropagation neural network model

T cell receptor repertoire as a novel indicator for identification and immune surveillance of patients with severe obstructive sleep apnea

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