Articles: regulatory-t-lymphocytes.
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Multicenter Study Clinical Trial
The predictive value of regulatory T cells on glucocorticoid sensitivity in patients with immune thrombocytopenia: a multicentre, prospective clinical study.
Glucocorticoids (GC) are used as the first-line treatment of immune thrombocytopenia (ITP), but 10-20% of patients are insensitive to them. Regulatory T cells (Tregs) can maintain immune tolerance in autoimmune diseases. The present research pooled 55 patients with newly diagnosed ITP and 44 healthy volunteers from seven hospitals. ⋯ There were no obvious changes in the level of CD4+ Tregs. These findings support that the level of CD8+ CD25str+ Tregs and its subgroups have a predictive value in judging the sensitivity to GC among patients with ITP. Trial registration: www.chictr.org.cn; ChiCTR-OON-17014165.
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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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Multicenter Study
Ex-vivo characterization of regulatory T cells in pulmonary tuberculosis patients, latently infected persons, and healthy endemic controls.
Regulatory T cells (Treg) are an essential arm of adaptive immunity not only in tolerance and autoimmunity but also in infectious diseases. In Tuberculosis (TB), it has been suggested that the frequency of Tregs is higher in the blood of TB patients when compared to healthy controls with subsequent decline after treatment. However, with the discovery that FOXP3, the hallmark marker of Tregs, is not exclusive to Tregs and the lack of specific markers for Tregs, it has been a challenge to fully understand the role of Tregs in TB. ⋯ The findings in this study showed that the association of Treg frequency with TB disease depends on the phenotypic markers used. While the frequency of CD4(+)CD25(+/hi) T cells was higher in TB patients compared to LTBI individuals, there was no difference in the frequency of CD4(+)CD25(+)FOXP3(+)CD127(lo) Treg among TB, LTBI, or EC. However, delineation of Tregs into active and naïve subsets revealed a significant increase in FOXP3 expression in active primed Tregs (CD4(+)CD25(+)FOXP3(+)CD127(lo)CD45RO(+)Ki-67(+)) of TB patients compared to LTBI and EC; and a significantly higher frequency of resting primed (CD45RO(+)Ki-67(-)) Treg in QuantiFERON negative EC compared to TB patients. After treatment completion, there was a significant decline in the frequency of active primed Treg, median (IQR) from 12.4% (9.5-21.9) of Tregs to 9.3% (7.0-12.2); P = 0.003 Wilcoxon signed rank test. We conclude that Treg subsets may be differentially regulated and expressed in TB disease, cure, and infection.
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Multicenter Study
Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma.
Daratumumab targets CD38-expressing myeloma cells through a variety of immune-mediated mechanisms (complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and antibody-dependent cellular phagocytosis) and direct apoptosis with crosslinking. These mechanisms may also target nonplasma cells that express CD38, which prompted evaluation of daratumumab's effects on CD38-positive immune subpopulations. Peripheral blood (PB) and bone marrow (BM) from patients with relapsed/refractory myeloma from 2 daratumumab monotherapy studies were analyzed before and during therapy and at relapse. ⋯ The majority of patients demonstrated these broad T-cell changes, although patients with a partial response or better showed greater maximum effector and helper T-cell increases, elevated antiviral and alloreactive functional responses, and significantly greater increases in T-cell clonality as measured by T-cell receptor (TCR) sequencing. Increased TCR clonality positively correlated with increased CD8(+) PB T-cell counts. Depletion of CD38(+) immunosuppressive cells, which is associated with an increase in T-helper cells, cytotoxic T cells, T-cell functional response, and TCR clonality, represents possible additional mechanisms of action for daratumumab and deserves further exploration.
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Cancer Immunol. Immunother. · Jun 2016
Randomized Controlled Trial Multicenter StudyDisease progression in recurrent glioblastoma patients treated with the VEGFR inhibitor axitinib is associated with increased regulatory T cell numbers and T cell exhaustion.
Recurrent glioblastoma is associated with a poor overall survival. Antiangiogenic therapy results in a high tumor response rate but has limited impact on survival. Immunotherapy has emerged as an efficient treatment modality for some cancers, and preclinical evidence indicates that anti-VEGF(R) therapy can counterbalance the immunosuppressive tumor microenvironment. ⋯ Our results suggest that axitinib treatment in patients with recurrent glioblastoma has a favorable impact on immune function. At the time of acquired resistance to axitinib, we documented further enhancement of a preexisting immunosuppression. Further investigations on the role of axitinib as potential combination partner with immunotherapy are necessary.