ORCID Profile
0000-0003-4566-0793
Current Organisation
Northumbria University
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Publisher: Public Library of Science (PLoS)
Date: 30-04-2008
Publisher: Springer Science and Business Media LLC
Date: 14-11-2008
DOI: 10.1007/S00262-008-0620-4
Abstract: Lenalidomide (Revlimid CC-5013) and pomalidomide (CC-4047) are IMiDs proprietary drugs having immunomodulatory properties that have both shown activity in cancer clinical trials lenalidomide is approved in the United States for a subset of MDS patients and for treatment of patients with multiple myeloma when used in combination with dexamethasone. These drugs exhibit a range of interesting clinical properties, including anti-angiogenic, anti-proliferative, and pro-erythropoietic activities although exact cellular target(s) remain unclear. Also, anti-inflammatory effects on LPS-stimulated monocytes (TNF-alpha is decreased) and costimulatory effects on anti-CD3 stimulated T cells, (enhanced T cell proliferation and proinflammatory cytokine production) are observed. These drugs also cause augmentation of NK-cell cytotoxic activity against tumour-cell targets. Having shown that pomalidomide confers T cell-dependent adjuvant-like protection in a preclinical whole tumour-cell vaccine-model, we now show that lenalidomide and pomalidomide strongly inhibit T-regulatory cell proliferation and suppressor-function. Both drugs inhibit IL-2-mediated generation of FOXP3 positive CTLA-4 positive CD25high CD4+ T regulatory cells from PBMCs by upto 50%. Furthermore, suppressor function of pre-treated T regulatory cells against autologous responder-cells is abolished or markedly inhibited without drug related cytotoxicity. Also, Balb/C mice exhibit 25% reduction of lymph-node T regulatory cells after pomalidomide treatment. Inhibition of T regulatory cell function was not due to changes in TGF-beta or IL-10 production but was associated with decreased T regulatory cell FOXP3 expression. In conclusion, our data provide one explanation for adjuvant properties of lenalidomide and pomalidomide and suggest that they may help overcome an important barrier to tumour-specific immunity in cancer patients.
Publisher: Human Kinetics
Date: 04-2023
Abstract: Purpose : Exercise has transient effects on the immune system that could influence infection risk and tissue recovery after exercise. Little is known about how the menstrual cycle interacts with the immune responses to acute exercise. This exploratory study sought to evaluate the effect of menstrual-cycle phase on peripheral blood mononuclear cell counts before and immediately after a bout of intense aerobic exercise. Methods : Seven naturally menstruating women (age: 27 [3] y) completed three 5-km cycling time trials coinciding with the early-follicular, late-follicular, and mid-luteal stage, confirmed by hormonal measurement. Venous blood s les were taken and examined for the presence of immune cell types using flow cytometry. Results : Reductions in circulating CCR7 + CD45RA + naïve CD4 + T cells, CD4 + CD25 + regulatory T cells, and CD56 + CD57 + natural killer cells observed during the early-follicular phase were attenuated when exercise was performed during the late-follicular phase. Similarly, reductions in circulating CD56 + CD57 + natural killer cells and CD14 + TLR4 + monocytes following exercise in the early-follicular phase were abolished when exercise was performed in the midluteal phase. Conclusions : These preliminary findings indicate that the effect of acute high-intensity exercise on immune-cell mobilization and activation varies across the menstrual cycle, potentially impacting the anti-inflammatory effects of regulatory T cells and the cell-mediated effects of both natural killer CD57 + cells and monocytes expressing TLR4.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Stephen Todryk.