Articles: regulatory-t-lymphocytes.
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J. Reprod. Immunol. · Jun 2018
Inhibition of pregnancy-associated granulocytic myeloid-derived suppressor cell expansion and arginase-1 production in preeclampsia.
Myeloid-derived suppressor cells (MDSCs) expand in maternal peripheral blood and cord blood during normal pregnancy to maintain maternal-fetal tolerance. Here we investigated the expansion and function of MDSCs in preeclampsia (PE) patients. Maternal peripheral blood mononuclear cells (PBMCs) and cord blood mononuclear cells (CBMCs) were sampled from healthy pregnant women and PE patients, and analyzed for the frequencies and phenotypes of MDSCs and T cells. ⋯ There was no significant difference in the frequency of Treg cells between normal pregnancies and PE patients, but the pregnancy-associated increase of granulocytic MDSCs (G-MDSCs), but not monocytic MDSCs (M-MDSCs), in both PBMCs and CBMCs was markedly inhibited in PE patients. Furthermore, serum levels of Arg-1, an important effector molecule for G-MDSC were significantly reduced in PE patients compared to healthy pregnant women. In conclusion, the lack of G-MDSC expansion is a most notable feature of PE-associated immune-cell alterations, suggesting that restoring G-MDSCs may have the potential to treat PE.
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Intensive care medicine · May 2018
Multicenter Study Observational StudyCell-surface signatures of immune dysfunction risk-stratify critically ill patients: INFECT study.
Cellular immune dysfunctions, which are common in intensive care patients, predict a number of significant complications. In order to effectively target treatments, clinically applicable measures need to be developed to detect dysfunction. The objective was to confirm the ability of cellular markers associated with immune dysfunction to stratify risk of secondary infection in critically ill patients. ⋯ This study confirms our previous findings that three cell surface markers can predict risk of subsequent secondary infection, demonstrates the feasibility of standardized multisite flow cytometry and presents a tool which can be used to target future immunomodulatory therapies.
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Inhibition of programmed cell death-1 (PD-1) and its ligand programmed death ligand 1 (PD-L1) by using an immune checkpoint inhibitor has emerged as a promising immunotherapy for NSCLC. The correlation of PD-L1 expression in tumor cells with treatment outcomes has been reported in many pivotal trials; however, the relationship remains unclear. Here, we demonstrate that those patients with both high density of PD-1-positive CD8 and PD-L1-positive CD4-positive CD25-positive (PD-1hi PD-L1hi) regulatory T cells (Tregs) have a better response to PD1/PD-L1 blockade. ⋯ Our findings suggested that the density of PD-L1-positive CD4-positive CD25-positive Tregs in the tumor microenvironment can serve as a diagnostic factor to supplement PD-L1 expression in tumor cells and predict the response to PD-1/PD-L1 blockade immunotherapy in NSCLC.
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The prognostic role of PDL1 expression, CD8+ and FoxP3+ lymphocytes in vulvar melanomas has not been studied. We correlated PDL1 expression and CD8+ and FoxP3+ immune infiltrates with clinicopathologic variables and patient outcomes in a series of 75 vulvar melanomas. Tumoral PDL1 expression (>5%) was seen in 23% of cases. ⋯ In conclusion, our study shows that, independent from tumor thickness, an increased density of peritumoral FoxP3+ lymphocytes may positively impact survival in a subset of vulvar melanomas. Tumoral PDL1 expression correlated with tumoral as well as peritumoral CD8+ and FoxP3+ lymphocytes, supportive of an adaptive immune response. Although the frequency of PDL1 expression is low in vulvar melanoma, its expression may identify a subset of vulvar melanoma that might respond to immunotherapy.