scholarly journals The Cellular Effects of Nicotine and Tobacco Particulate Matter on Monoamine Transporters

2021 ◽  
Author(s):  
◽  
Kirsty Maree Danielson
Keyword(s):  
Smoking Cessation ◽  
Molecular Biology ◽  
Protein Expression ◽  
Mrna Expression ◽  
Cigarette Smoke ◽  
Ex Vivo ◽  
Dependent Manner ◽  
Monoamine Transporters ◽  
Monoamine Transporter ◽  
Smoking Addiction

<p>Cigarette smoking causes nearly 6 million deaths worldwide every year (WHO, 2011). Current smoking cessation therapies available to the public are only marginally effective (Jorenby, 2006; Balfour et al., 2000), partly due to our incomplete understanding of the molecular biology of smoking addiction. The majority of studies examining the molecular biology of smoking addiction have focused on nicotine alone. However, there is a growing body of evidence that non-nicotinic components of cigarette smoke contribute to smoking addiction. Nicotine has previously been shown to modulate the function of the monoamine transporters, but studies in the literature are often contradictory and this effect is not completely understood (see Danielson et al., 2011 for review). Furthermore, very few studies have examined the effects of non-nicotinic components of tobacco smoke on the monoamine transporters. This thesis has examined the effects of nicotine and a tobacco extract (TPM) on the dopamine, serotonin, and norepinephrine transporters (DAT, NET, and SERT). Changes in monoamine transporter function, protein expression, and mRNA expression were measured ex vivo in discrete regions of the rat brain following chronic and acute in vivo nicotine and TPM treatment, and in vitro nicotine and TPM treatment. We found that nicotine and TPM affect monoamine transporter function, in a time- and dose-dependent manner, and that intact whole brain circuitry is required for these effects to be seen. In particular, nicotine (0.35 mg/kg) and TPM (containing 0.35 mg/kg nicotine) significantly decreased DAT function in the NAc at 30 min. This effect did not result in a corresponding decrease in DAT protein expression and was mediated by nicotinic receptors containing β2 subunits. Furthermore, TPM caused some changes in monoamine transporter function and mRNA expression that were not observed with nicotine alone. In functional studies this effect was particularly seen in the striatum of rats treated with nicotine (0.35 mg/kg) or TPM (containing 0.35 mg/kg nicotine). Overall these data demonstrate that nicotine affects monoamine transporter function in a nicotinic receptor-dependent manner, and that nicotine and TPM have different effects on monoamine transporter function and expression. This is the first study to examine the effects of TPM on monoamine transporter function, and supports previous evidence of a contribution of non-nicotinic components of cigarette smoke to neuroadaptations related to smoking. Findings from this study contribute to knowledge on the molecular biology of smoking addiction, which could in future lead to the development of more effective smoking cessation therapies.</p>

scholarly journals The Cellular Effects of Nicotine and Tobacco Particulate Matter on Monoamine Transporters

2021 ◽  
Author(s):  
◽  
Kirsty Maree Danielson
Keyword(s):  
Smoking Cessation ◽  
Molecular Biology ◽  
Protein Expression ◽  
Mrna Expression ◽  
Cigarette Smoke ◽  
Ex Vivo ◽  
Dependent Manner ◽  
Monoamine Transporters ◽  
Monoamine Transporter ◽  
Smoking Addiction

<p>Cigarette smoking causes nearly 6 million deaths worldwide every year (WHO, 2011). Current smoking cessation therapies available to the public are only marginally effective (Jorenby, 2006; Balfour et al., 2000), partly due to our incomplete understanding of the molecular biology of smoking addiction. The majority of studies examining the molecular biology of smoking addiction have focused on nicotine alone. However, there is a growing body of evidence that non-nicotinic components of cigarette smoke contribute to smoking addiction. Nicotine has previously been shown to modulate the function of the monoamine transporters, but studies in the literature are often contradictory and this effect is not completely understood (see Danielson et al., 2011 for review). Furthermore, very few studies have examined the effects of non-nicotinic components of tobacco smoke on the monoamine transporters. This thesis has examined the effects of nicotine and a tobacco extract (TPM) on the dopamine, serotonin, and norepinephrine transporters (DAT, NET, and SERT). Changes in monoamine transporter function, protein expression, and mRNA expression were measured ex vivo in discrete regions of the rat brain following chronic and acute in vivo nicotine and TPM treatment, and in vitro nicotine and TPM treatment. We found that nicotine and TPM affect monoamine transporter function, in a time- and dose-dependent manner, and that intact whole brain circuitry is required for these effects to be seen. In particular, nicotine (0.35 mg/kg) and TPM (containing 0.35 mg/kg nicotine) significantly decreased DAT function in the NAc at 30 min. This effect did not result in a corresponding decrease in DAT protein expression and was mediated by nicotinic receptors containing β2 subunits. Furthermore, TPM caused some changes in monoamine transporter function and mRNA expression that were not observed with nicotine alone. In functional studies this effect was particularly seen in the striatum of rats treated with nicotine (0.35 mg/kg) or TPM (containing 0.35 mg/kg nicotine). Overall these data demonstrate that nicotine affects monoamine transporter function in a nicotinic receptor-dependent manner, and that nicotine and TPM have different effects on monoamine transporter function and expression. This is the first study to examine the effects of TPM on monoamine transporter function, and supports previous evidence of a contribution of non-nicotinic components of cigarette smoke to neuroadaptations related to smoking. Findings from this study contribute to knowledge on the molecular biology of smoking addiction, which could in future lead to the development of more effective smoking cessation therapies.</p>

C-Mpl Is Not Expressed or Functional At Detectable Levels on Primary Chronic Lymphocytic Leukemia (CLL) Tumor Samples

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2849-2849
Author(s):  
Robert D Loberg ◽  
Shen-Wu Wang ◽  
Scott D Patterson ◽  
Ian McCaffery
Keyword(s):  
Flow Cytometry ◽  
Protein Expression ◽  
Mrna Expression ◽  
Functional Response ◽  
Disease Risk ◽  
Ex Vivo ◽  
Employment Equity ◽  
Equity Ownership ◽  
Significant Expression ◽  
Stimulation Of

Abstract Abstract 2849 The development of thrombocytopenia is associated with progression of CLL to a more advanced stage and is commonly used to classify CLL into the higher disease risk categories. It has been estimated that 5% of CLL patients will present with associated immune thrombocytopenia purpura (ITP) and immune mediated destruction can exacerbate thrombocytopenia related to bone marrow infiltration. Thromopoietin (TPO) mimetics stimulate platelet production though activation of the thrombopoietin receptor (c-Mpl) on megakaryocytes and are currently indicated for chronic ITP. In principle, this approach could be considered for treatment of ITP in CLL patients. In order to rule out the possibility that c-Mpl is functionally expressed in CLL tumor cells; we analyzed expression and TPO-dependent function in primary patient samples. We have developed assays for the analysis of c-Mpl expression on the surface of B-cells in CLL patient samples and to assess functional response to ex-vivo stimulation of theses primary samples with TPO. Peripheral blood was collected from CLL patients and mononuclear cells isolated by Ficoll separation. This cohort included treatment naïve CLL samples (n=57) and CLL samples collected from subjects undergoing active treatment (n=30). CLL cells were analyzed by flow cytometry and identified based upon viability and CD5+/CD19+ expression. c-Mpl expression was measured using a novel c-Mpl-specific monoclonal antibody that was shown to be specific for c-Mpl by flow cytometry. Residual platelets associated with individual PBMC aliquot served as an internal control for c-Mpl expression. To investigate c-Mpl function, CLL cells were stimulated with rhTPO (10 ng/mL for 10 min) and induction of pSTAT5 was measured to assess a functional response to ex-vivo stimulation of TPO. In addition c-Mpl mRNA expression was surveyed in CLL by using mRNA microarray analyses to correlate c-Mpl mRNA expression with protein and functional expression of c-Mpl. Robust c-Mpl protein expression was observed in platelets from normal and CLL patients (fold over control -normal: 31.90 ± 6.39, CLL: 26.76 ± 6.57; mean ± 95%CI), no significant expression of c-Mpl was observed on CD5+/CD19+ CLL cells (fold over control −1.06 ± 0.021; mean ± 95%CI). No induction of STAT5 phosphorylation was detected in B-cell CLL cells in any of the samples stimulated with TPO (fold over control - normal: 0.90 ± 0.02, CLL: 1.04 ± 0.034; mean ± 95%CI). Microarray analysis of the CLL samples demonstrated c-Mpl mRNA expression levels equivalent to background across all CLL samples analyzed (intensity score −10.3 ± 3.0; mean ± 95%CI). In conclusion, we demonstrated a lack of cell surface c-Mpl protein expression in CLL cells. The additional data suggesting the lack of evidence for significant expression of c-Mpl mRNA expression supports the hypothesis that CLL cells do not express c-Mpl and unlikely to be stimulated in patients treated with TPO mimetics. This hypothesis will need to be tested in an appropriate clinical trial to assess the potential benefits of TPO mimetics for the treatment of thrombocytopenia in CLL patients. Disclosures: Loberg: Amgen: Employment, Equity Ownership. Wang:Amgen: Employment, Equity Ownership. Patterson:Amgen: Employment, Equity Ownership. McCaffery:Amgen: Employment, Equity Ownership.

scholarly journals Novel Cell Type–Specific Antiviral Mechanism of Interferon γ Action in Macrophages

2001 ◽  
Vol 193 (4) ◽  
pp. 483-496 ◽  
Author(s):  
Rachel M. Presti ◽  
Daniel L. Popkin ◽  
Megan Connick ◽  
Susanne Paetzold ◽  
Herbert W. Virgin
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Interferon Γ ◽  
Murine Cytomegalovirus ◽  
Dependent Manner ◽  
Cell Type ◽  
Mcmv Infection ◽  
A Cell ◽  
Ifn Γ ◽  
Factor Α

Interferon (IFN)-γ and macrophages (Mϕ) play key roles in acute, persistent, and latent murine cytomegalovirus (MCMV) infection. IFN-γ mechanisms were compared in embryonic fibroblasts (MEFs) and bone marrow Mϕ (BMMϕ). IFN-γ inhibited MCMV replication in a signal transducer and activator of transcription (STAT)-1α–dependent manner much more effectively in BMMϕ (∼100-fold) than MEF (5–10-fold). Although initial STAT-1α activation by IFN-γ was equivalent in MEF and BMMϕ, microarray analysis demonstrated that IFN-γ regulates different sets of genes in BMMϕ compared with MEFs. IFN-γ inhibition of MCMV growth was independent of known mechanisms involving IFN-α/β, tumor necrosis factor α, inducible nitric oxide synthase, protein kinase RNA activated (PKR), RNaseL, and Mx1, and did not involve IFN-γ–induced soluble mediators. To characterize this novel mechanism, we identified the viral targets of IFN-γ action, which differed in MEF and BMMϕ. In BMMϕ, IFN-γ reduced immediate early 1 (IE1) mRNA during the first 3 h of infection, and significantly reduced IE1 protein expression for 96 h. Effects of IFN-γ on IE1 protein expression were independent of RNaseL and PKR. In contrast, IFN-γ had no significant effects on IE1 protein or mRNA expression in MEFs, but did decrease late gene mRNA expression. These studies in primary cells define a novel mechanism of IFN-γ action restricted to Mϕ, a cell type key for MCMV pathogenesis and latency.

scholarly journals Peroxisome Proliferator-Activated Receptor-γ(PPAR-γ) Agonists Attenuate the Profibrotic Response Induced by TGF-β1 in Renal Interstitial Fibroblasts

2007 ◽  
Vol 2007 ◽  
pp. 1-7 ◽  
Author(s):  
Weiming Wang ◽  
Feng Liu ◽  
Nan Chen
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Kidney Diseases ◽  
Smooth Muscle Actin ◽  
Tissue Growth ◽  
Time Dependent ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ

Background.Studies have shown that peroxisome proliferator-activated receptor-γ(PPAR-γ) agonists could ameliorate renal fibrotic lesions in both diabetic nephropathy and nondiabetic chronic kidney diseases. In order to elucidate the antifibrotic mechanism of PPAR-γagonists, we investigated the effects of PPAR-γactivation on TGF-β1-induced renal interstitial fibroblasts.Methods.In rat renal interstitial fibroblasts (NRK/49F), the mRNA expression of TGF-β1-inducedα-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), fibronectin (FN) and collagen type III (Col III) were observed by reverse transcriptase-polymerase chain reaction (RT-PCR). The protein expressions of FN and Smads were observed by Western blot.Results.In NRK/49F, TGF-β1 enhanced CTGF, FN and Col III mRNA expression in a dose- and time-dependent manner.α-SMA, CTGF, FN and Col III mRNA and FN protein expression in 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2)-troglitazone- and ciglitazone-pretreated groups, respectively, were significantly decreased compared with the TGF-β1-stimulated group. TGF-β1 (5 ng/mL) enhanced p-Smad2/3 protein expression in a time-dependent manner. Compared with the TGF-β1-stimulated group, p-Smad2/3 protein induced by TGF-β1 in PPAR-γagonists-pretreated groups significantly decreased with no statistical difference amongst the three pretreated groups.Conclusion.PPAR-γagonists could inhibit TGF-β1-induced renal fibroblast activation, CTGF expression and ECM synthesis through abrogating the TGF-β1/Smads signaling pathway.

Adiponectin inhibits tissue factor expression and enhances tissue factor pathway inhibitor expression in human endothelial cells

2008 ◽  
Vol 100 (08) ◽  
pp. 291-300 ◽  
Author(s):  
Yi-Jian Chen ◽  
Li-Qun Zhang ◽  
Guang-Ping Wang ◽  
Hui Zeng ◽  
Ben Lü ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Protein Expression ◽  
Mrna Expression ◽  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Tnf Α ◽  
Tissue Factor Pathway ◽  
Expression And Activity

SummaryTissue factor (TF) plays a pivotal role in thrombus formation and atherogenesis in acute coronary syndrome. Tissue factor pathway inhibitor (TFPI) is a specific physiological inhibitor of TF/ FVIIa complex that regulates TF-induced coagulation. Adiponectin (Adp) is an adipocyte-specific adipocytokine with anti-atherogenic and anti-diabetic properties. Adp inhibits inflammatory cytokine and adhesion molecules expression, and it can prevent endothelial dysfunction. In this study, we investigated the effects of Adp on tumor necrosis factor-α (TNF-α)-induced expression of TF and TFPI in human umbilical vein endothelial cells (HU-VECs), and the signaling transduction pathways involved. It was found that Adp significantly inhibited both TF protein expression and activity in TNF-α-stimulated HUVECs. In the meanwhile, it increased TFPI protein expression and activity for about two folds. Adp also inhibited TF mRNA expression induced by TNF-α, but had no effect on TFPI mRNA expression. The inhibitory effect of Adp onTNF-α-inducedTF expression was prevented by pretreatment with Rp-cAMPs, a PKA inhibitor. Adp increased intracellular cAMP content and PKA activity levels in a dose-dependent manner. Phosphorylation of IκB-α was decreased by Adp, but phosphorylation of p44/42MAPK, SAPK/ JNK, and p38MAPK were not affected. These results suggested that Adp inhibits TF expression through inhibition of a PKA dependent nuclear factor- κB (NF-κB) signaling pathway. It was also found that adiponectin promoted Akt and AMP-activated protein kinase phosphorylation. The inhibitory effect of Adp on TNF-α-induced TF synthesis was abrogated in part by pretreatment with the PI3kinase inhibitor LY 294002, suggesting that Akt activation might inhibit TF expression induced by TNF-α. The inhibitory effect of Adp is almost completely abrogated by inhibition of both the cAMP/PKA pathway and PI3K/Akt pathway. In conclusion, our data indicated that inhibition of NF-κB through stabilization of IκB-α and activation of Akt phosphorylation may mediate the inhibitory effect of Adp on TF expression; but the enhancement effect of Adp on the TFPI production might occur via translational rather than transcriptional regulation.

scholarly journals Effects of selenium on selenoprotein synthesis and antioxidant parameters of bovine mammary epithelial cells

2018 ◽  
Vol 63 (No. 8) ◽  
pp. 313-322
Author(s):  
Guo Yongmei ◽  
Gong Jian ◽  
Shi Binlin ◽  
Guo Xiaoyu ◽  
Yan Sumei
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Dependent Manner ◽  
Promoting Effect ◽  
Bovine Mammary Epithelial Cells ◽  
Antioxidant Parameters ◽  
Mrna And Protein Expression ◽  
Dose Dependent

This study aimed to investigate the effects of selenium (Se) on the selenoproteins synthesis and antioxidant parameters of bovine mammary epithelial cells (BMECs). The experiment was conducted as a single factor completely randomized design to explore the effect of different levels of Se supplementation (0, 10, 20, 50, and 100 nmol/l) on selenoproteins synthesis and antioxidant parameters of BMECs, and to screen the appropriate dose of Se supplementation ensuring a better antioxidant function. Se supplementation increased cell proliferation, the activities of glutathione peroxidase (GPx) and superoxide dismutase, total antioxidant capacity and seleoprotein P (SelP) content, and decreased reactive oxygen species and malondialdehyde levels in a dose-dependent manner. Se supplementation of 50–100 nmol/l had a better effect. Se supplementation also increased thioredoxin reductase (TrxR) activity in a dose-dependent manner, and Se supplementation of 20–50 nmol/l had a better promoting effect. The dose-dependent response between Se supplementation and mRNA and protein expression of GPx1 and TrxR1, as well as SelP mRNA expression was also observed in this experiment. The mRNA and protein expression of GPx1 was up-regulated with the addition of 50–100 nmol/l Se, and the mRNA expression of TrxR1 and SelP was up-regulated with the addition of 20–100 nmol/l Se. Results indicated that Se supplementation of 50 nmol/l had a better promoting effect on the selenoproteins synthesis and antioxidant parameters of BMECs.

scholarly journals The sodium iodide symporter gene and its regulation by cytokines found in autoimmunity

1998 ◽  
Vol 158 (3) ◽  
pp. 351-358 ◽  
Author(s):  
RA Ajjan ◽  
PF Watson ◽  
C Findlay ◽  
RA Metcalfe ◽  
M Crisp ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Ex Vivo ◽  
Tnf Alpha ◽  
Thyroid Cell ◽  
Dependent Manner ◽  
Ifn Gamma ◽  
Mrna Tissue Distribution ◽  
Nis Gene ◽  
Rat Thyroid

Iodide concentration by the thyroid gland, an essential step for thyroid hormone synthesis, is mediated by the Na+/I- symporter (NIS). To identify factors that may regulate this process, we have studied NIS gene expression in the Fisher rat thyroid cell line (FRTL-5) by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) technique. Increasing concentrations of bovine TSH (0.1, 1, 10, 50 and 100 mU/l), with or without tumour necrosis factor-alpha (TNF alpha), interferon-gamma (IFN gamma) or interleukin-1 alpha (IL-1 alpha) were added to FRTL-5 cells previously deprived of TSH for a minimum of 5 days. RNA was extracted and samples were studied for NIS expression. TSH enhanced NIS mRNA expression in a dose-dependent manner, with induction evident at 0.1 mU/l, reaching a peak at 50 mU/l, an effect detected after 6 h of stimulation, but not in the first 2 h. Both TNF alpha and, to a lesser extent, IL-1 alpha inhibited basal and TSH-induced NIS expression. High concentrations of IFN gamma also downregulated TSH-stimulated NIS mRNA expression. Using the same technique, we also investigated NIS mRNA tissue distribution in two male and one female Wistar rats. High levels of NIS expression were detected in the thyroid, stomach, and mammary gland, lower levels were found in the intestine, adipose tissue and liver, borderline levels were expressed in the salivary gland, and no expression was detected in the kidneys. In summary, we have shown that TSH upregulates rat NIS gene expression in vitro, and this induction can be modulated by cytokines. Analysis of the distribution of rat NIS mRNA ex vivo demonstrated variable levels of NIS transcription in different tissue samples.

Ethanol Extract of Achillea fragrantissima Enhances Angiogenesis through Stimulation of VEGF Production

2020 ◽  
Vol 21 ◽  
Author(s):  
Hana M. Hammad ◽  
Amer Imraish ◽  
Maysa Al-Hussaini ◽  
Malek Zihlif ◽  
Amani A. Harb ◽  
...  
Keyword(s):  
Wound Healing ◽  
Rural Communities ◽  
Ex Vivo ◽  
Ethanol Extract ◽  
Aortic Ring ◽  
Treated Group ◽  
Control Group ◽  
Dependent Manner ◽  
Achillea Fragrantissima

Objective: Achillea fragrantissima L. (Asteraceae) is a traditionally used medicinal herb in the rural communities of Jordan. Methods: The present study evaluated the efficacy of the ethanol extract of this species on angiogenesis in both, ex vivo using rat aortic ring assay and in vivo using rat excision wound model. Results: In concentrations of 50 and 100 µg/ml, the ethanol extract showed angiogenic stimulatory effect and significantly increased length of capillary protrusions around aorta rings of about 60% in comparison to those of untreated aorta rings. In MCF-7 cells, the ethanol extract of A. fragrantissima stimulates the production of VEGF in a dose-dependent manner. 1% and 5% of ethanol extract of A. fragrantissima containing vaseline based ointment was applied on rat excision wounds for six days and was found to be effective in wound healing and maturation of the scar. Both preparations resulted in better wound healing when compared to the untreated control group and vaseline-treated group. This effect was comparable to that induced by MEBO, the positive control. Conclusion: The results indicate that A. fragrantissima has a pro-angiogenic effect, which may act through the VEGF signaling pathway.

scholarly journals Targeting CD38 is lethal to Breg-like chronic lymphocytic leukemia cells and Tregs, but restores CD8+ T-cell responses

2020 ◽  
Vol 4 (10) ◽  
pp. 2143-2157 ◽  
Author(s):  
Alak Manna ◽  
Timothy Kellett ◽  
Sonikpreet Aulakh ◽  
Laura J. Lewis-Tuffin ◽  
Navnita Dutta ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Cd8 T Cells ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Xenograft Model ◽  
Lymphocytic Leukemia ◽  
Dependent Manner

Abstract Patients with chronic lymphocytic leukemia (CLL) are characterized by monoclonal expansion of CD5+CD23+CD27+CD19+κ/λ+ B lymphocytes and are clinically noted to have profound immune suppression. In these patients, it has been recently shown that a subset of B cells possesses regulatory functions and secretes high levels of interleukin 10 (IL-10). Our investigation identified that CLL cells with a CD19+CD24+CD38hi immunophenotype (B regulatory cell [Breg]–like CLL cells) produce high amounts of IL-10 and transforming growth factor β (TGF-β) and are capable of transforming naive T helper cells into CD4+CD25+FoxP3+ T regulatory cells (Tregs) in an IL-10/TGF-β-dependent manner. A strong correlation between the percentage of CD38+ CLL cells and Tregs was observed. CD38hi Tregs comprised more than 50% of Tregs in peripheral blood mononuclear cells (PBMCs) in patients with CLL. Anti-CD38 targeting agents resulted in lethality of both Breg-like CLL and Treg cells via apoptosis. Ex vivo, use of anti-CD38 monoclonal antibody (mAb) therapy was associated with a reduction in IL-10 and CLL patient-derived Tregs, but an increase in interferon-γ and proliferation of cytotoxic CD8+ T cells with an activated phenotype, which showed an improved ability to lyse patient-autologous CLL cells. Finally, effects of anti-CD38 mAb therapy were validated in a CLL–patient-derived xenograft model in vivo, which showed decreased percentage of Bregs, Tregs, and PD1+CD38hiCD8+ T cells, but increased Th17 and CD8+ T cells (vs vehicle). Altogether, our results demonstrate that targeting CD38 in CLL can modulate the tumor microenvironment; skewing T-cell populations from an immunosuppressive to immune-reactive milieu, thus promoting immune reconstitution for enhanced anti-CLL response.

Sign in / Sign up

Export Citation Format

Share Document