The role of senescent T cells in immunopathology

Covre, Luciana Polaco; Maeyer, Roel P.H. De; Gomes, Daniel Cláudio Oliveira; Akbar, Arne N.

doi:10.1111/acel.13272

Cited by 63 publications

(59 citation statements)

References 85 publications

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“… 56–62 Tregs eliminate the immune response by expressing CTLA-4, which binds CD80/CD86, competes with CD28, and blocks the T cells activation. 63–65 The inhibition of immune checkpoints prevents immune exhaustion and leads to the reactivation of the anticancer immune response, 66–69 consistent with this analysis. This analysis obtained closely negative correlations between SLC6A1 and T cell exhaustion (CTLA-4, PD-L1)/Monocyte (CD86) in liver cancer tissues, but not in normal liver tissue, providing the immune regulatory functions of SLC6A1 expression in tumorigenesis of HCC.…”

Section: Discussionsupporting

confidence: 81%

A miR-212-3p/SLC6A1 Regulatory Sub-Network for the Prognosis of Hepatocellular Carcinoma

Zhang

Wang²,

et al. 2021

CMAR

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Introduction Hepatocellular carcinoma (HCC) is a liver cancer with a poor prognosis. Owing to the complexity and limited pathogenic mechanism research on HCC, the molecular targeted therapy has been hindered. Methods In this study, we categorized transcriptome data into low-Myc and high-Myc expression groups in 365 HCC samples, screened the differentially expressed RNAs, including 441 DE-lncRNAs, 99 DE-miRNAs and 612 DE-mRNAs, constructed a lncRNA-miRNA-mRNA regulatory network, and selected a hub triple regulatory network through cytoHubba analysis. Through Gene ontology and KEGG pathway, a hub regulatory network was particularly enriched in the “Wnt signaling pathway” and “Cytochrome P450-arranged by substrate type” by Metascape. The prognostic genes in the hub regulatory network were evaluated by the RNA expression analysis, Kaplan–Meier (KM) survival analysis, and correlation analysis. Results The results showed that miR-212-3p/SLC6A1 axis was a potential prognostic model for HCC. Furthermore, IHC analysis showed down-regulated expression of SLC6A1 in HCC tissues and Alb-Cre;Myc mouse liver cancer tissues. The genetics and epigenetic analysis indicated that SLC6A1 expression was negatively correlated with DNA methylation. Immune infiltration analysis showed a negative relation between SLC6A1 and T cell exhaustion/monocyte in liver cancer tissues. Conclusion In summary, the study revealed that miR-212-3p/SLC6A1 axis could serve as a crucial therapeutic target for HCC.

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Section: Discussionsupporting

confidence: 81%

A miR-212-3p/SLC6A1 Regulatory Sub-Network for the Prognosis of Hepatocellular Carcinoma

Zhang

Wang²,

et al. 2021

CMAR

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“…In addition to the common features mentioned above, senescent T cells show distinct surface markers. Senescent T cells lose the expression of costimulatory receptors CD27/CD28 but express CD57 and KLRG-1, which indicates replicative senscent [2] , [3] , [4] . Senescent T cells also show a terminally differentiated phenotype with the downregulation of the chemokine receptors CCR7 and CD45RO but the upregulation of CD45RA [ 17 , 22 , 23 ].…”

Section: Characteristics and Potential Roles Of Senescent T Cells In Tumoursmentioning

confidence: 99%

“…The principle features of exhausted T cells is the elevated inhibitory receptors, including programmed cell death protein 1 (PD-1), T cell immunoglobulin and mucin domain containing-3 (Tim-3), and lymphocyte activation gene-3 (LAG-3) with impaired cytotoxicity and effector cytokine production [1] . Senescent T cells have a distinct phenotypes including downregulated expression of the costimulatory molecules CD27 and CD28, and high expression of CD57, killer cell lectin-like receptor subfamily G member 1 (KLRG-1), and CD45RA [2] , [3] , [4] . They share common features with senescent somatic cells such as DNA damage, declines in proliferation and activation, but are able to produce high amounts of proinflammatory cytokines [5] .…”

Section: Introductionmentioning

confidence: 99%

Senescent T cells: a potential biomarker and target for cancer therapy

Zhang

Xue

et al. 2021

EBioMedicine

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The failure of T cells to eradicate tumour cells in the tumour microenvironment is mainly due to the dysfunction of T cells. Senescent T cells, with defects in proliferation and effector functions, accumulate in ageing, chronic viral infections, and autoimmune disorders where antigen stimulation persists. Increasing evidence suggests that inducing T cell senescence is a key strategy used by malignant tumours to evade immune surveillance. In this review, we summarize the general features, functional regulation, and signalling network of senescent T cells in tumour development and highlight their potential as prognostic biomarkers in multiple cancer treatments, including chemotherapy, radiotherapy, and immunotherapy. Moreover, we discuss possible therapeutic strategies for preventing or rejuvenating senescence in tumour-specific T cells. Understanding these critical issues may provide novel strategies to enhance cancer immunotherapy.

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“…This process is probably hampered in elderly patients. 189 Nonetheless, important questions also arise in patients with IgA immunodeficiency or mild immunodeficiencies and patients with IgA nephropathy even though they respond to remdesivir therapy. 163 Strong antibody responses against the SARS-CoV-2 virus were detected in patients that quickly recover from the infection.…”

Section: De Sanctis Et Almentioning

confidence: 99%

“…In B cells, clonal expansion occurs in convalescence with a dramatic expansion of IgA positive B cells, and then, other B cells start producing IgG antibodies with neutralizing ability. This process is probably hampered in elderly patients 189 . Nonetheless, important questions also arise in patients with IgA immunodeficiency or mild immunodeficiencies and patients with IgA nephropathy even though they respond to remdesivir therapy 163 …”

Section: Antigen Presentation and Adaptive Immune Response Virus Escapementioning

confidence: 99%

Coronavirus infection: An immunologists' perspective

et al. 2021

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Coronaviruses (CoVs) are a collection of enveloped viruses with non-segmented, positive-sense single-stranded RNA genomes with distinctive crown-like spikes that protrude from the capsid of helical symmetry. 1 They have a remarkably long RNA genome and a particular replication strategy. In this complex family, several members attack different species causing several diseases that can end up in death. In November 2002, in China, a severe acute respiratory syndrome coronavirus (SARS-CoV) was identified. It promptly spread to other countries. There were around 8000 confirmed cases, and the mortality rate was 9.6%. 2 Then, another member of the family, Middle East respiratory syndrome coronavirus (MERS-CoV), appeared in Saudi Arabia in 2012 and later emerged in South Korea in 2015. The confirmed cases of MERS-CoV exceeded 2000, with a mortality rate of ∼35%. 2 In 2019, another member of the family was identified, SARS-CoV-2. 3 The number of infected people and the mortality rate still grow continuously. Infected elderly individuals with comorbidities exhibit the worst outcomes. There are now several vaccines against SARS-CoV-2 approved for emergency use by the regulatory offices of different countries.The coronavirus genome is formed by 2 UTR sites, 5′ and 3′, the replicase, the spike (Spike), the envelope E (Envelope), the M (Membrane), the N (Nucleocapsid) and

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The role of senescent T cells in immunopathology

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 63 publications

References 85 publications

A miR-212-3p/SLC6A1 Regulatory Sub-Network for the Prognosis of Hepatocellular Carcinoma

A miR-212-3p/SLC6A1 Regulatory Sub-Network for the Prognosis of Hepatocellular Carcinoma

Senescent T cells: a potential biomarker and target for cancer therapy

Coronavirus infection: An immunologists' perspective

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