FoxP3 Expression In Patients Research Articles

The expression level of FOXP3 and CD25 in Iraqi patients with post burn injuries

Introduction and Aim: Regulatory T cells (Treg) are characterized by CD25+ expression and Foxp3+ transcription factors which is a characteristic marker for these cells. This study aimed to investigate the expression of Foxp3 in patients with post-burn injuries in Baghdad, Iraq. Materials and Methods: The study samples included 38 persons divided into two groups: the first group included patients with Total Body surface area (TBSA) of burn less than 45% (TBSA 45 %), and patients with TBSA of burn more than 45 % (TBSA 45%). The control group included healthy individuals (n=10). The expression of FOXP3 and CD25 of Treg cells was measured by using flow cytometry and data obtained was statistically analyzed. Results: The result of the study showed a significant increase in Foxp3 and CD25 expression in Treg cells that were isolated from peripheral blood in patients with TBSA 45 % and TBSA 45% following day 1 and day 5 of the burn injury in contrast to the control group, and the expression level of Foxp3 was (35.674, 63.768 ,16.147) respectively after the first day of the burn, while the expression level of Foxp3 after the fifth day of the burn was (39.588, 47.275, 16.1470) respectively. Similarly, the levels of CD5 recorded for patients in TBSA 45%, TBSA45% and control group on day1 was 29.747, 43.447 and 16.793 respectively, while on day 5 it was 33.870.197 and 16.793, for the three groups, respectively. Conclusion: The increase of Foxp3 and CD25 expression in Treg cells isolated from burn patients has an important effect in enhancing the activity of Treg cells in inhibiting the immune response.

Regulatory T cells limit opportunistic colonization of Staphylococcus aureusto promote lesion resolution in cutaneous leishmaniasis

Abstract The severity and responsiveness to treatment in L. braziliensis patients is influenced by a variety of factors, including microbiota and cytolytic T cells. Recently, we studied the skin microbiome in patients and demonstrated that high levels of S. aureus are associated with delayed healing in patients. To understand how S. aureus might influence cutaneous leishmaniasis, we studied the immune responses in mice following colonization with a S. aureus isolate from a L. braziliensis patient. Colonization of the skin with S. aureus alone induced a dominant type-17 response as well as an accumulation of Foxp3 T regulatory cells, and subsequent infection of mice with L. braziliensis led to increased IL-17 dependent pathology. Unexpectedly, transient depletion of total Tregs or RORγtin Foxp3 Tregs in S. aureus colonized mice increased IFN-γ and decreased the IL-17A response in skin. These mice exhibited increased pathology, which was accompanied by epidermal cell death and loss of barrier integrity. Additionally, the mice had substantially more S. aureus in the skin, and in the lymph nodes. In mice colonized with S. aureus and infected with L. braziliensis partial reduction led to a substantial increase in disease and a higher burden of S. aureus. Consistent with these results, in a transcriptional analysis of lesions from L. braziliensis patients, we found that low Foxp3 expression in patients had increased expression of cytolytic genes and IFN-γ, increased S. aureus in the lesions and had a delay in lesion resolution compared to patients with high Foxp3. Taken, together, these results suggest that in L. braziliensis patients Tregs are critical to regulate type-1 responses that in the context of S. aureus can promote more severe disease.

Combination Therapy with Fexofenadine and Fluticasone Propionate Increases FOXP3 Expression in Patients with Allergic Rhinitis

Combination Therapy with Fexofenadine and Fluticasone Propionate Increases FOXP3 Expression in Patients with Allergic Rhinitis

GPR Expression in Intestinal Biopsies From SCT Patients Is Upregulated in GvHD and Is Suppressed by Broad-Spectrum Antibiotics.

Microbiota can exert immunomodulatory effects by short-chain fatty acids (SCFA) in experimental models of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT). Therefore we aimed to analyze the expression of SCFAs sensing G-protein coupled receptor GPR109A and GPR43 by quantitative PCR in 338 gastrointestinal (GI) biopsies obtained from 199 adult patients undergoing allo-SCT and assessed the interaction of GPR with FOXP3 expression and regulatory T cell infiltrates. GPR expression was strongly upregulated in patients with stage II-IV GvHD (p=0.000 for GPR109A, p=0.01 for GPR43) and at the onset of GvHD (p 0.000 for GPR109A, p=0.006 for GPR43) and correlated strongly with FOXP3 and NLRP3 expression. The use of broad-spectrum antibiotics (Abx) drastically suppressed GPR expression as well as FOXP3 expression in patients’ gut biopsies (p=0.000 for GPRs, FOXP3 mRNA and FOXP3+ cellular infiltrates). Logistic regression analysis revealed treatment with Abx as an independent factor associated with GPR and FOXP3 loss. The upregulation of GPRs was evident only in the absence of Abx (p=0.001 for GPR109A, p=0.014 for GPR43) at GvHD onset. Thus, GPR expression seems to be upregulated in the presence of commensal bacteria and associates with infiltration of FOXP3+ T regs, suggesting a protective, regenerative immunomodulatory response. However, Abx, which has been shown to induce dysbiosis, interferes with this protective response.

Effect of intraoperative blood transfusion on Treg and FOXP3 in patients with digestive tract malignancies and different ABO blood types

BackgroundBlood transfusion can cause immunosuppression and lead to worse outcomes in patients with digestive tract malignancies; however, the specific mechanism behind this is not completely understood. One theory is that increased numbers of regulatory CD3+CD4+CD25+FOXP3+ T cells (Tregs) and forkhead box protein-3 mRNA (FOXP3) expression in the blood after transfusion contribute to these outcomes. The effect of blood transfusion on immune function in patients with different ABO blood types is variable. This study investigates the effect of intraoperative blood transfusion on the number of Tregs and the expression of FOXP3 in the blood of patients with different ABO blood types and digestive tract malignancies.MethodsPatients with digestive tract malignancies who underwent radical resection and received intraoperative blood transfusion were divided into four groups according to their blood types:blood group A, blood group B, blood group O and blood group AB (n = 20 for each group). Blood was collected from all patients before surgery, immediately after transfusion, 1 day after transfusion, and 5 days after transfusion. The number of Tregs was measured by flow cytometry. The expression of FOXP3 was detected by real time reverse transcription polymerase chain reaction (RT-PCR).ResultsThere was no significant difference in the number of Tregs or expression of FOXP3 mRNA among patients with different blood types before surgery. However, the number of Tregs and the expression of FOXP3 increased after blood transfusion in all blood type groups. This increase was especially evident and statistically significant on the first day after blood transfusion when compared with measures obtained before the surgery. Measures returned to the preoperative level five days after surgery. There were significant differences in the increase of Tregs and expression of FOXP3 among patients with different blood types. The greatest increase was seen in patients with blood group B and the least in blood group A.ConclusionsIntraoperative blood transfusion can lead to an increase in blood Tregs and FOXP3 expression in patients with digestive tract malignancies. Increases were greatest on the first day after surgery and differed among patients with different blood types. Increases were greatest in blood type B and least in blood type A.

Long non‑coding RNA RP11‑340F14.6 promotes a shift in the Th17/Treg ratio by binding with P2X7R in juvenile idiopathic arthritis.

Long non‑coding RNA (lncRNAs) have been identified to play important roles in multiple human diseases via the regulation of cell proliferation, cell invasion, or cell death. However, little is known about the role of lncRNAs in the process of shifts in the Th17/Treg ratio during the progression of juvenile idiopathic arthritis (JIA). The aim of the present study was to determine the role of lncRNA RP11‑340F14.6 in the shifting of the Th17/Treg ratio in JIA. The distribution of the T cell subgroup was detected by flow cytometry in peripheral blood mononuclear cells from patients with JIA and healthy controls. It was found that the expression of lncRNA RP11‑340F14.6 was upregulated, and to positively correlate with that of retinoic acid‑related orphan receptor gammat (RORγt), and to negatively correlate with Foxp3 expression in patients with JIA. RP11‑340F14.6 induced the expression of its neighbor, P2X7R. Through a P2X7R‑independent approach, this lncRNA was also found to play a pivotal role in stimulating Th17 differentiation and simultaneously suppressing Treg distribution. Taken together, the findings of the present study demonstrate that RP11‑340F14.6 specifically binds to P2X7R, which results in the continuous activation of P2X7R. Thus, RP11‑340F14.6 may serve as a promising therapeutic target for the treatment of JIA.

Nanocurcumin improves regulatory T-cell frequency and function in patients with multiple sclerosis

BackgroundMultiple sclerosis is a chronic incapacitating disease of the central nervous system, it has been reported that the disturbance in the development and function of Treg subpopulations is associated with the disability status in the RRMS. Accordingly, in the current study, the objective was to specify nanocurcumin effects on Treg cells frequency, and function in patients with RRMS. Methods and materials50 patients with RRMS were enrolled in this study in which 25 were treated for at least six months with nanocurcumin capsules while the other half received placebo capsules as the control group. The blood sample was collected prior to the administration of nanocurcumin and placebo capsules and following six months. At baseline and after a six-month treatment, the frequency of Treg lymphocytes, the expression of transcription factor related to these cells and the secretion levels of cytokines were assessed by flowcytometry, real-time PCR and ELISA, respectively. ResultsA significant reduction was observed in the proportion of peripheral Treg cell frequency, and the levels of TGF-β, IL-10 and FoxP3 expression in patients with RRMS. Our data revealed that the frequency of Treg cells (p = .0027), the expression of FoxP3 (p = .0005), TGF-β (p = .0005), and IL-10 (p = .0002) and the secretion levels of the TGF-β (p = .033), and IL-10 (p = .029) in cultured PBMCs are increased in nanocurcumin-treated group compared to placebo group. ConclusionThe results of the current work indicated that nanocurcumin is capable of restoring the frequency and function of Treg cells in MS patients.

The prognostic role of CD68 and FoxP3 expression in patients with primary central nervous system lymphoma.

The prognostic role of CD68 and FoxP3 in primary central nervous system lymphoma (PCNSL) has not been evaluated. Thus, we examined the prognostic significance of CD68 and FoxP3 expression in tumor samples of 76 newly diagnosed immunocompetent PCNSL patients. All patients were treated initially with high-dose methotrexate (HD-MTX)-based chemotherapy, and 16 (21.1%) patients received upfront autologous stem cell transplantation (ASCT) consolidation. High expression of CD68 (>55 cells/high-power field) or FoxP3 (>15 cells/high-power field) was observed in 10 patients, respectively. High CD68 expression was associated with inferior overall survival (OS) and progression-free survival (PFS) in multivariate analysis (P=0.023 and P=0.021, respectively). In addition, we performed subgroup analysis based on upfront ASCT. High CD68 expression was also associated with inferior OS and PFS in multivariate analysis (P=0.013 and P<0.001, respectively) among patients who did not receive upfront ASCT (n=60), but not in patients who received upfront ASCT. The expression of FoxP3 was not significantly associated with survival. Therefore, we identified a prognostic significance of high CD68 expression in PCNSL, which suggests a need for further clinical trials and biological studies on the role of PCNSL tumor microenvironment.

Helios expression and Foxp3 TSDR methylation of IFNy+ and IFNy- Treg from kidney transplant recipients with good long-term graft function.

BackgroundThere is circumstantial evidence that IFNy+ Treg might have clinical relevance in transplantation. IFNy+ Treg express IFNy receptors and are induced by IFNy. In the present study we investigated in kidney transplant recipients with good long-term stable graft function the absolute cell counts of IFNy+ Treg subsets and whether their expression of Foxp3 is stable or transient.MethodHelios expression determined by eight-color-fluorescence flow cytometry and methylation status of the Foxp3 Treg specific demethylation region (TSDR) served as indicators for stability of Foxp3 expression. Methylation status was investigated in enriched IFNy+ and IFNy- Treg preparations originating from peripheral blood using high resolution melt analysis. A total of 136 transplant recipients and 52 healthy controls were studied.ResultsProportions of IFNy+ Treg were similar in patients and healthy controls (0.05% and 0.04% of all CD4+ lymphocytes; p = n.s.). Patients also had similar absolute counts of IFNy producing Helios+ and Helios- Treg (p = n.s.). Most of the IFNy+ and IFNy- Treg in transplant recipients had a methylated Foxp3 TSDR, however, there was a sizeable proportion of IFNy+ and IFNy- Treg with demethylated Foxp3 TSDR. Male and female patients showed more frequently methylated IFNy+ and IFNy- Treg than male and female controls (all p<0.05).ConclusionsKidney transplant recipients with good long-term stable graft function have similar levels of IFNy+ Treg as healthy controls. IFNy+ and IFNy- Treg subsets in patients consist of cells with stable and cells with transient Foxp3 expression; however, patients showed more frequently methylated IFNy+ and IFNy- Treg than controls. The data show increased levels of Treg subsets with stable as well as transient Foxp3 expression in patients with stable allograft acceptance compared to healthy controls.

Critical link between glycogen synthase kinase 3β and forkhead box P3 in patients with chronic rhinosinusitis with nasal polyps

Critical link between glycogen synthase kinase 3β and forkhead box P3 in patients with chronic rhinosinusitis with nasal polyps

Programmed cell death protein 1 expression is an independent prognostic factor in gastric cancer after curative resection.

Programmed cell death protein 1 (PD-1) and its ligand PD-L1 downregulate T cell activation and are related to immune tolerance. The aim of this study was to clarify the significance of PD-1 and PD-L1 expression and to analyze the relationships among PD-1, PD-L1, and Foxp3 expression in gastric cancer. A total of 105 patients who underwent curative gastrectomy for stage II/III gastric cancer were included in this study. PD-1, PD-L1, and Foxp3 expression were examined by immunohistochemistry and related to prognostic factors by univariate and multivariate analyses. PD-1 expression was correlated with both PD-L1 and Foxp3 expression. Disease-free survival (DFS) was significantly poorer in PD-1-positive patients than in PD-1-negative patients (3-year DFS, 36.1 % vs. 64.7 %, respectively; p < 0.05). Overall survival also tended to be poorer in PD-L1-positive patients than in PD-L1-negative patients. Univariate analysis identified sex, T factor, lymphatic invasion, and PD-1 positivity as significant predictors of poor DFS. Multivariate analysis confirmed male sex, lymphatic invasion, and positive PD-1 expression as independent prognostic indicators. PD-1 expression is associated with a poor prognosis and is correlated with PD-L1 and Foxp3 expression in patients with gastric cancer.

Abnormalities in the T cell receptor Vδ repertoire and Foxp3 expression in refractory anemia with ringed sideroblasts.

Immune dysregulation has been implicated in myelodysplastic syndrome (MDS) pathogenesis. Refractory anemia with ringed sideroblasts (RARS) is a low-risk subtype of MDS. Our previous study has reported an abnormal γδ T cell receptor (TCR) repertoire in patients with intermediate or high-risk MDS. To characterize the status of T cell immunity in RARS, we investigated the distribution and clonality of the TCR Vδ repertoire and the expression of Foxp3 in patients with RARS. The number of expressed Vδ subfamily members in the RARS group (4.8±2.25) was significantly lower than that in the control group (7.6±0.52, p=0.0012). A significantly lower expression frequency for the Vδ4 (p=0.007), Vδ5 (p=0.0049) and Vδ7 subfamilies (p=0.0225) could be detected in the RARS group. The most frequent clonally expanded T cell subfamily member in the RARS group was Vδ7 (100%, 3/3). Foxp3 mRNA expression was significantly lower and higher than that in the controls in 60% and 40% RARS patients, respectively. In conclusion, marked restriction of the TCR Vδ subfamily expression pattern and great heterogeneity in Foxp3 expression were characteristics found in RARS. These results provide data regarding the immunodeficiency and immune reactive characteristics of patients with RARS, which may provide a basis for immunotherapy options.

T regulatory cells (TREG)(TCD4+CD25+FOXP3+) distribution in the different clinical forms of leprosy and reactional states.

BACKGROUNDLeprosy is characterized histologically by a spectrum of different granulomatous skin lesions, reflecting patients' immune responses to Mycobacterium leprae. Although CD4+CD25+ FoxP3+ T regulatory cells are pivotal in the immuneregulation, presence, frequency, and distribution of Tregs in leprosy, its reactional states have been investigated in few studies.OBJECTIVESThis study aimed to verify the frequency and distribution of regulatory T cells in different clinical forms and reactional states of leprosy.METHODSWe performed an immunohistochemical study on 96 leprosy cases [Indeterminate (I): 9 patients; tuberculoid tuberculoid: 13 patients; borderline tuberculoid: 26 patients; borderline borderline: 3 patients; borderline lepromatous: 8 patients; lepromatous lepromatous: 27 patients; reversal reaction: 8 patients; and erythema nodosum leprosum: 2 patients].RESULTSFoxP3-positive cells were present in 100% of the cases with an average density of 2.82% of the infiltrate. Their distribution was not related to granulomatous structures or special locations. There was a statistically significant increment of FoxP3 expression in patients with leprosy reversal reactions when compared with patients presenting with type I leprosy (P= 0.0228); borderline tuberculoid leprosy (P = 0.0351) and lepromatous leprosy (P = 0.0344).CONCLUSIONSThese findings suggest that Tregs play a relevant role in the etiopathogenesis of leprosy, mainly in type I leprosy reaction.

Foxp3 gene expression in oral lichen planus: A clinicopathological study

CD4+CD25+ Forkhead‑box protein 3 (Foxp3+) regulatory T cells are important in oral lichen planus (OLP). The present study aimed to investigate Foxp3 expression in CD4+CD25+ T cells of peripheral blood mononuclear cells and oral lesions in patients diagnosed with OLP, who were grouped as OLP subtype, duration and relapse. Using quantitative polymerase chain reaction (qPCR), western blotting and immunohistochemistry, Foxp3 expression levels in explants of oral lesions and CD4+CD25+ T cells from 32 patients with OLP were measured and compared, with 10 healthy subjects as the control group. Foxp3 mRNA expression levels in the explants of oral lesions and circulating CD4+CD25+ T cells in patients with OLP were significantly higher than those in the control group (P<0.05). In patients with clinically erosive lesions, Foxp3 mRNA expression was significantly lower in circulating CD4+CD25+ T cells and tissue explants compared to patients with reticular lesions (P<0.01 and P<0.05, respectively), and lowest in patients with a history of OLP of >1 year or with a history of relapse (P<0.05 and P<0.01, respectively). Foxp3 protein levels in reticular OLP were significantly higher than those in erosive OLP and the control group. The incidence of Foxp3 protein expression in OLP tissues was 36.24±18.92 and 10.44±6.51% in normal oral mucosa (P=0.019). Atrophic/erosive OLP lesions showed a higher proportion of Foxp3‑expressing cells than that of reticular OLP lesions (P<0.05). This study indicated that Foxp3 expression in patients with OLP is associated with the severity and duration of the disorder, suggesting altered immune suppression in the development, clinical course and responsiveness to treatment.

Foxp3 expression in patients with non-small cell lung cancer.

e18059 Background: Lung cancer is rarely cured by the current therapeutic approaches. Although numerous studies have implicated Foxp3 positive T regulatory cells in cancer pathogenesis, the role of Foxp3 in lung cancer pathogenesis remains unknown. Methods: We determined Foxp3 expression, using immunohistochemistry in 44 NSCLC tissue specimens, 20 samples from adjacent non neoplastic lung parenchyma and 5 normal lung tissue specimens. Immunohistochemical reactivity was graded on a scale of 0–3 according to intensity of staining and percentage of immunopositive cells. Foxp3 expression in cancer cells was categorized in three groups (high vs median vs low) using as a cut-off point the 33rd and 66th percentile. The total score for each slide was the sum of the intensity and distribution (between 0 and 6). Statistical analysis was performed with SPSS 17.0. Results: Nuclear Foxp3 immunostaining was detected in al tissues assessed. Foxp3 expression levels were higher in neoplastic cells than in adjacent non neoplastic tissue and normal lung parenchyma. Moreover, Foxp3 expression in tumor cells correlated with lymphocytic Foxp3-immunopositivity and the presence of lymph node metastasis. Furthermore, Foxp3 lymphocytic expression was negatively associated with the age of the patients. Conclusions: Foxp3 is overexpressed in NSCLC cells and tumor infiltrating lymphocytes. Moreover, tumor Foxp3 expression correlates with lymph node metastasis while lymphocytic Foxp3 levels may be age-related.

The Regulation of FOXP3 Expression by the Treatment of TGF-β and the Modification of DNA Methylation in Lung Cancer Cell Lines

Background: Transcription factor FOXP3 characterizes the thymically derived regulatory T cells. FOXP3 is expressed by cancer cell itself and FOXP3 expression was induced by TGF-β treatment in pancreatic cancer cell line. However, the expression of FOXP3 expression is not well known in patients with lung cancer. This study was conducted to investigate the expression of FOXP3 in patients with lung cancer and to investigate the regulation of FOXP3 expression by the treatment of TGF- β and DNA methyltransferase inhibitor in lung cancer cell lines. Methods: FOXP3 expression in the tissue of patients with resected non-small cell lung cancer (NSCLC) was evaluated by immunohistochemistry. The regulation of FOXP3 expression was investigated by Western blot and RT-PCR after lung cancer cell lines were stimulated with TGF-β1 and TGF-β2. The regulation of FOXP3 expression was also investigated by RT-PCR and flow cytometry after lung c ancer cell lines were treated with DNA methyltransferase inhibitor (5-AZA-dC). Results: FOXP3 expression was confirmed in 27% of patients with NSCLC. In NCI-H460 cell line, TGF-β2 decreased FOXP3 mRNA and protein expressions. In A549 cell line, both TGF-β1 and TGF-β2 decreased FOXP3 mRNA and protein expressions. 5-AZA-dC increased FOXP3 mRNA expression in NCI-H460 and A549 cell lines. Moreover, 5-AZA-dC increased intracellular FOXP3 protein expression in A549 cell lines. Conclusion: It was shown that FOXP3 is expressed by cancer cell itself in patients with NSCLC. Treatment of TGF- β2 and DNA methyltransferase inhibitor seems to be associated with the regulation of FOXP3 expression in lung cancer cell lines.

Reduced frequency of CD4+CD25HIGHFOXP3+ cells and diminished FOXP3 expression in patients with Common Variable Immunodeficiency: A link to autoimmunity?

Common Variable Immunodeficiency (CVID) is a primary immunodeficiency disease characterized by defective immunoglobulin production and often associated with autoimmunity. We used flow cytometry to analyze CD4(+)CD25(HIGH)FOXP3(+) T regulatory (Treg) cells and ask whether perturbations in their frequency in peripheral blood could underlie the high incidence of autoimmune disorders in CVID patients. In this study, we report for the first time that CVID patients with autoimmune disease have a significantly reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells in their peripheral blood accompanied by a decreased intensity of FOXP3 expression. Notably, although CVID patients in whom autoimmunity was not diagnosed had a reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells, FOXP3 expression levels did not differ from those in healthy controls. In conclusion, these data suggest compromised homeostasis of CD4(+)CD25(HIGH)FOXP3(+) cells in a subset of CVID patients with autoimmunity, and may implicate Treg cells in pathological mechanisms of CVID.

CD4+ CD25+ FoxP3+ T-cell infiltration and heme oxygenase-1 expression correlate with tumor grade in human gliomas.

Regulatory T-cells play an important role in the regulation of the immune response and the mediation of dominant immunologic tolerance. We have previously shown that these cells are elevated in tumors and blood of patients with glioblastoma multiforme. Heme oxygenase-1, a rate-limiting enzyme in heme catabolism, has also been shown to accumulate during glioma progression and to play a critical role in FoxP3 mediated immune suppression. In this study, we investigated the correlation between FoxP3 and HO-1 expression in patients with various grades of astrocytoma (WHO grade II-IV). Using qualitative and quantitative reverse transcriptase-polymerase chain reaction and quantitative flow cytometry analyses, we analyzed FoxP3 and HO-1 expression in 19 patients with different grades of astrocytoma. We observed the highest level of FoxP3 expression in patients with grade IV tumors (11.54 +/- 1.95%) vs. grade III (6.74 +/- 0.19%) or grade II (2.53 +/- 0.11%) (P < 0.05). Moreover, in grade IV tumors, the frequency of HO-1 mRNA expression in CD4+ CD25+ cells was 11.8 +/- 2.45% vs. 7.42 +/- 0.31% in grade III and 2.33 +/- 0.12% in grade II. Tumor infiltrating Treg stained positively with anti-HO-1 antibody. The expression of HO-1 correlated with CD4+ CD25+ FoxP3+ infiltration (r = 0.966). Our results confirm that HO-1 expressing Treg accumulate during glioma progression. This study also suggests that HO-1 mRNA expression is linked to the induction of Foxp3 in CD4+ CD25+ glioma infiltrating Treg. These findings support the suppressive role played by regulatory T-cells in the growth of malignant brain tumors.