scholarly journals Immune checkpoint molecules in pregnancy: Focus on regulatory T cells

2020 ◽  
Vol 50 (2) ◽  
pp. 160-169 ◽  
Author(s):  
Yong‐Hong Zhang ◽  
Hai‐Xiang Sun
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Molecules ◽  
In Pregnancy

scholarly journals Immune‐checkpoint molecules on regulatory T‐cells as a potential therapeutic target in head and neck squamous cell cancers

2020 ◽  
Vol 111 (6) ◽  
pp. 1943-1957 ◽  
Author(s):  
Susumu Suzuki ◽  
Tetsuya Ogawa ◽  
Rui Sano ◽  
Taishi Takahara ◽  
Daisuke Inukai ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Therapeutic Target ◽  
Potential Therapeutic Target ◽  
Immune Checkpoint Molecules

scholarly journals Immune checkpoint blockade impairs immunosuppressive mechanisms of regulatory T cells in B-cell lymphoma

2021 ◽  
Vol 14 (9) ◽  
pp. 101170
Author(s):  
Vera Bauer ◽  
Fatima Ahmetlić ◽  
Nadine Hömberg ◽  
Albert Geishauser ◽  
Martin Röcken ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
B Cell ◽  
Immune Checkpoint ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade

Regulatory T cells in pregnancy

2006 ◽  
Vol 28 (1) ◽  
pp. 31-39 ◽  
Author(s):  
Ana Claudia Zenclussen
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
In Pregnancy

scholarly journals O4 Mechanisms of lung cancer hyper-progression promoted by PD-1 immune checkpoint blockade

2020 ◽  
Vol 8 (Suppl 2) ◽  
pp. A5.1-A5
Author(s):  
A Martinez-Usatorre ◽  
E Kadioglu ◽  
C Cianciaruso ◽  
B Torchia ◽  
J Faget ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Immune Checkpoint ◽  
Immune Cell ◽  
Immune Checkpoint Blockade ◽  
Genetically Engineered ◽  
Checkpoint Blockade ◽  
Therapeutic Benefits ◽  
Angiopoietin 2

BackgroundImmune checkpoint blockade (ICB) with antibodies against PD-1 or PD-L1 may provide therapeutic benefits in patients with non-small cell lung cancer (NSCLC). However, most tumours are resistant and cases of disease hyper-progression have also been reported.Materials and MethodsGenetically engineered mouse models of KrasG12Dp53null NSCLC were treated with cisplatin along with antibodies against angiopoietin-2/VEGFA, PD-1 and CSF1R. Tumour growth was monitored by micro-computed tomography and the tumour vasculature and immune cell infiltrates were assessed by immunofluorescence staining and flow cytometry.ResultsCombined angiopoietin-2/VEGFA blockade by a bispecific antibody (A2V) modulated the vasculature and abated immunosuppressive macrophages while increasing CD8+effector T cells in the tumours, achieving disease stabilization comparable or superior to cisplatin-based chemotherapy. However, these immunological responses were unexpectedly limited by the addition of a PD-1 antibody, which paradoxically enhanced progression of a fraction of the tumours through a mechanism involving regulatory T cells and macrophages. Elimination of tumour-associated macrophages with a CSF1R-blocking antibody induced NSCLC regression in combination with PD-1 blockade and cisplatin.ConclusionsThe immune cell composition of the tumour determines the outcome of PD-1 blockade. In NSCLC, high infiltration of regulatory T cells and immunosuppressive macrophages may account for tumour hyper-progression upon ICB.Disclosure InformationA. Martinez-Usatorre: None. E. Kadioglu: None. C. Cianciaruso: None. B. Torchia: None. J. Faget: None. E. Meylan: None. M. Schmittnaegel: None. I. Keklikoglou: None. M. De Palma: None.

scholarly journals Imaging Changes and Immune-Checkpoint Expression on T Cells in Bronchoalveolar Lavage Fluid from Patients with Pulmonary Sarcoidosis

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1231
Author(s):  
Yasuaki Kotetsu ◽  
Toyoshi Yanagihara ◽  
Kunihiro Suzuki ◽  
Hiroyuki Ando ◽  
Daisuke Eto ◽  
...  
Keyword(s):  
T Cells ◽  
Bronchoalveolar Lavage ◽  
Immune Checkpoint ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Pulmonary Sarcoidosis ◽  
Immune Checkpoint Molecules ◽  
Ct Findings ◽  
Programmed Cell Death 1 ◽  
Spontaneous Improvement

Sarcoidosis is a systemic, granulomatous disease caused by unknown immunological abnormalities. The organs most vulnerable to sarcoidosis are the lungs. Patients often resolve spontaneously, but the lungs can also be severely affected. Although details regarding prognostic factors in sarcoidosis patients with lung involvement remain unclear, several reports have suggested that immune checkpoint molecules are involved in the pathogenesis of sarcoidosis. In this study, we divided sarcoidosis patients into two groups based on chest computed tomography (CT) findings and compared immune checkpoint molecules expressed on T cells in bronchoalveolar lavage fluid (BALF) in the two groups, using flow cytometry. We found elevated programmed cell death 1 (PD-1) or T cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) expression on T cells in BALF in patients with spontaneous improvement in CT findings, compared with those in patients without improvement in CT findings. In conclusion, our study implies that PD-1 or TIM-3 expression on T cells in BALF may be a prognostic factor for pulmonary lesions in sarcoidosis.

scholarly journals Regulatory T Cells in Pregnancy Adverse Outcomes: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Samantha Green ◽  
Marina Politis ◽  
Kathrine S. Rallis ◽  
Alba Saenz de Villaverde Cortabarria ◽  
Athina Efthymiou ◽  
...  
Keyword(s):  
Systematic Review ◽  
T Cells ◽  
Regulatory T Cells ◽  
Pregnant Women ◽  
Peripheral Blood ◽  
Meta Analysis ◽  
Adverse Outcomes ◽  
Case Control Studies ◽  
Inconsistency Index ◽  
In Pregnancy

BackgroundSeveral studies report the role of Regulatory T-cells (Tregs) in the pathophysiology of pregnancy adverse outcomes.ObjectiveThe aim of this systematic review and meta-analysis was to determine whether there is an association between regulatory T cell levels and pregnancy adverse outcomes (PAOs), including pre-eclampsia and preterm birth (PTB).MethodLiterature searches were conducted in PubMed/MEDLINE, Embase, and Cochrane CENTRAL databases. Inclusion criteria were original articles (clinical trials, case-control studies and cohort studies) comparing Tregs, sampled from the decidua or maternal blood, in healthy pregnant women versus women with pre-eclampsia or PTB. The outcome was standardised mean difference (SMD) in Treg numbers. The tau-squared (Tau²), inconsistency index (I²), and chi-squared (χ²) test quantified heterogeneity among different studies. Analyses were performed in RevMan software V.5.4.0 for Mac using a random-effects model with outcome data reported with 95% confidence intervals (CI). This study was prospectively registered with PROSPERO (CRD42020205469). PRISMA guidelines were followed.ResultsFrom 4,085 unique studies identified, 36 were included in qualitative synthesis, and 34 were included in quantitative synthesis (meta-analysis). In total, there were 1,783 participants in these studies: healthy controls=964, pre-eclampsia=759, PTB=60. Thirty-two studies compared Tregs in healthy pregnant women and women with pre-eclampsia, and 30 of these sampled Tregs from peripheral blood showing significantly higher Treg numbers in healthy pregnancies (SMD; 1.46; 95% CI, 1.03–1.88; I²=92%). Four studies sampled Tregs from the maternal decidua showing higher Tregs in healthy pregnancies (SMD, 0.76; 95% CI, -0.13–1.65; I²=84%). No difference was found in the number of Tregs between early versus late pre-eclampsia (SMD,-1.17; 95% CI, -2.79–0.44; I²=94%). For PTB, two studies compared Tregs sampled from the peripheral blood with a tendency for higher Tregs in healthy pregnancies but this did not reach significance (SMD, 2.18; 95% CI, -1.34–5.70; I²=96%). Subcohort analysis using Treg analysis (flow cytometry vs. qPCR vs. immunofluorescence tissue staining) showed similar associations.ConclusionLower Tregs in pregnancy, sampled from the maternal peripheral blood, are associated with pre-eclampsia. There is a need for further studies to confirm a relationship between low Tregs and PTB. As the precise mechanisms by which Tregs may mediate pre-eclampsia and PTB remain unclear, further fundamental research is necessary to elucidate the underlying processes and highlight the causative link.Systematic Review RegistrationPROSPERO, identifier CRD42020205469.

scholarly journals Impact of immune checkpoint molecules on FoxP3+ Treg cells and related cytokines in patients with acute and chronic brucellosis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hua-Li Sun ◽  
Xiu-Fang Du ◽  
Yun-Xia Tang ◽  
Guo-Qiang Li ◽  
Si-Yuan Yang ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Checkpoint ◽  
Treg Cells ◽  
Shanxi Province ◽  
Healthy Controls ◽  
Chronic Patients ◽  
Immune Checkpoint Molecules ◽  
Significant Difference ◽  
Acute Patients ◽  
Tgf Β1

Abstract Background The immunoregulatory functions of regulatory T cells (Tregs) in the development and progression of some chronic infectious diseases are mediated by immune checkpoint molecules and immunosuppressive cytokines. However, little is known about the immunosuppressive functions of Tregs in human brucellosis, which is a major burden in low-income countries. In this study, expressions of immune checkpoint molecules and Treg-related cytokines in patients with acute and chronic Brucella infection were evaluated to explore their impact at different stages of infection. Methods Forty patients with acute brucellosis and 19 patients with chronic brucellosis admitted to the Third People’s Hospital of Linfen in Shanxi Province between August 2016 and November 2017 were enrolled. Serum and peripheral blood mononuclear cells were isolated from patients before antibiotic treatment and from 30 healthy subjects. The frequency of Tregs (CD4+ CD25+ FoxP3+ T cells) and expression of CTLA-4, GITR, and PD-1 on Treg cells were detected by flow cytometry. Levels of Treg-related cytokines, including IL-35, TGF-β1, and IL-10, were measured by customised multiplex cytokine assays using the Luminex platform. Results The frequency of Tregs was higher in chronic patients than in healthy controls (P = 0.026) and acute patients (P = 0.042); The frequency of CTLA-4+ Tregs in chronic patients was significantly higher than that in healthy controls (P = 0.011). The frequencies of GITR+ and PD-1+ Tregs were significantly higher in acute and chronic patients than in healthy controls (P < 0.05), with no significant difference between the acute and chronic groups (all P > 0.05). Serum TGF-β1 levels were higher in chronic patients (P = 0.029) and serum IL-10 levels were higher in acute patients (P = 0.033) than in healthy controls. We detected weak correlations between serum TGF-β1 levels and the frequencies of Tregs (R = 0.309, P = 0.031) and CTLA-4+ Tregs (R = 0.302, P = 0.035). Conclusions Treg cell immunity is involved in the chronicity of Brucella infection and indicates the implication of Tregs in the prognosis of brucellosis. CTLA-4 and TGF-β1 may contribute to Tregs-mediated immunosuppression in the chronic infection stage of a Brucella infection.

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