Chronic activation profile of circulating CD8+ T cells in Sézary syndrome

Torrealba, Marina Passos; Manfrere, Kelly Cristina Gomes; Miyashiro, Denis; Lima, Jozely Francisca Mello; Oliveira, Lucas Ferrari de; Pereira, Newton Lindolfo; Cury‐Martins, Jade; Pereira, Juliana; Duarte, Alberto J. S.; Sato, Maria Notomi; Sanches, José Antônio

doi:10.18632/oncotarget.23334

Cited by 24 publications

(21 citation statements)

References 44 publications

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“…In SS patients, CD8þ cells down-regulate activation markers CD127/IL-7R and CD26 and remained unresponsive to IL-7 stimulation. This has been attributed to their chronic activation due to the massive proliferation of malignant CD4 þ T cells [53].…”

Section: Discussionmentioning

confidence: 99%

Divergent LAG-3 versus BTLA, TIGIT, and FCRL3 expression in Sézary syndrome

Anzengruber

Ignatova

Schlaepfer

et al. 2019

Leukemia & Lymphoma

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In S ezary syndrome (SS) impaired T-cell function and cytokine profile lead to immune evasion. Immune checkpoints non-redundantly regulate immune responses and targeting them is promising. We evaluated the expression of BTLA, CTLA-4, FCRL3, LAG-3, and TIGIT in tumor and nontumor SS T-cells.Compared to CD4þ T helper cells from ten healthy individuals, tumor cells of eight SS patients had a significant upregulation of BTLA (1.5-fold; p < .0001), FRCL3 (2.2-fold; p < .0028) and TIGIT (2.2-fold; p < .0003) expression. In contrast, we found a reduced expression of LAG-3þ cells in the blood of tumor patients (0.5-fold; p < .0014). Only weak alternations between tumor, non-tumor cells, and healthy controls were observed regarding CTLA-4 (0.5-fold; p < .2022). Our results show a diverse expression pattern of immune-regulatory molecules in SS patients. As these molecules are essential in the regulation of T-cell mediated tumor surveillance and defense, their specific targeting might be of clinical relevance.

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Section: Discussionmentioning

confidence: 99%

Divergent LAG-3 versus BTLA, TIGIT, and FCRL3 expression in Sézary syndrome

Anzengruber

Ignatova

Schlaepfer

et al. 2019

Leukemia & Lymphoma

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“…123 The aforementioned findings of increased CD26 − T lymphocytes are also present in CD8 + T cells. 129,130 The circulating CD26 − atypical lymphoid cells, known as Sézary cells, are considered a very sensitive and specific parameter for early detection 125,[131][132][133][134] in Sézary syndrome [134][135][136][137][138][139][140][141][142][143][144][145][146][147][148][149][150] and mycosis fungoides. 127,149,[151][152][153][154][155][156][157][158] Sézary cell levels are used for therapeutic monitoring, 125,[131][132][133][134]150 herald a change in clinical status, 131,153 and are a sensitive indicator of disease extent, prognosis, 127,159 and death.…”

Section: Cutaneous T-cell Lymphomamentioning

confidence: 99%

The role of Dipeptidyl Peptidase‐4 in cutaneous disease

Patel

Jones

Kridin

et al. 2020

Experimental Dermatology

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Dipeptidyl peptidase-4 (DPP4) is a multifunctional, type II transmembrane glycoprotein expressed on the cell surface of many tissues. 1,2 Its soluble form (aa 49-766) is also found in various bodily fluids (Figure 1). 3 CD26 is a cell surface marker with DPP4 enzymatic activity in its extracellular domain. For uniformity, we will use the term CD26 + or CD26 − to indicate the presence or absence of DPP4 as a cell surface marker but use DPP4 in reference to the enzyme and gene/protein expression. Dipeptidyl peptidase-4 is a serine exopeptidase, which cleaves X-proline or X-alanine dipeptide residues in the penultimate position from the NH 2-terminus of polypeptide substrates, including chemokines, neuropeptides and hormones. 4-6 The cysteine-rich domain of DPP4 interacts with the proteins of the extracellular matrix whilst the glycosylation-rich domain interacts with adenosine deaminase and caveolin-1 amongst others. 5,7,8 DPP4 inhibitors (DPP4i) are best known for their role in the treatment of diabetes mellitus due to their ability to deactivate incretins, such as glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. 9 The rise of DPP4 inhibitors, however, is also accompanied by undesired cardiovascular and dermatologic manifestations. 10-12 More recently, the role of DPP4 and its inhibition in various dermatoses including bullous pemphigoid, psoriasis and mycosis fungoides have been described. In this review, we sought to summarize the role of DPP4 expression, regulation, and inhibition in cutaneous diseases.

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“…1 The anti-tumoral immunity in SS is impaired, with CD8 + T cells showing chronic activation, anergic profile with an attenuated cytotoxic profile and impaired IL-7 responsiveness. 2 (Fig. 1c,d).…”

Section: Ifn-c Reshapes Monocyte Responsiveness In Sezary Syndromementioning

confidence: 91%

IFN‐γ reshapes monocyte responsiveness in Sezary syndrome

et al. 2020

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Figure 2 Monocytes of SS patients display altered chemokine and cytokine gene expression that can be reshaped by IFN-c. Expression of 84 genes in purified monocytes from healthy controls (HC, n = 3) and SS patients (n = 3) before and after IFN-c stimulation (25 ng/ml) was assessed by PCR array using a human Cytokines & Chemokines Array Kit. (a) Gene expression levels (normalized against four internal controls) in HC and SS were plotted in a scatter plot and differentially expressed genes (DEGs, considered as showing at least a twofold change in expression between SS and HC) were highlighted in green (down) or red (up). (b) Genes in the SS group whose expression after IFN-c addition showed at least a twofold change (stimulated vs. unstimulated conditions). Negative values/green bars indicate downregulated genes and positive values/red bars show upregulated ones. (c) CXCL9, CXCL10, and TLR3 expression assessed by conventional qPCR of purified monocytes unstimulated and upon IFN-c addition from HC (n = 3) and SS patients (n = 4)

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Chronic activation profile of circulating CD8+ T cells in Sézary syndrome

Cited by 24 publications

References 44 publications

Divergent LAG-3 versus BTLA, TIGIT, and FCRL3 expression in Sézary syndrome

Divergent LAG-3 versus BTLA, TIGIT, and FCRL3 expression in Sézary syndrome

The role of Dipeptidyl Peptidase‐4 in cutaneous disease

IFN‐γ reshapes monocyte responsiveness in Sezary syndrome

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