Prognostic potential of tumoral FOXP3 expression in relation with tumor-infiltrating regulatory T cells in human gastric cancers.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15036-e15036
Author(s):  
Jungho Suh ◽  
Wankyu EO ◽  
Si-Young Kim
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
T Cells ◽  
Regulatory T Cells ◽  
Cancer Cells ◽  
Prognostic Marker ◽  
Prognostic Significance ◽  
Foxp3 Expression ◽  
Cancer Tissue ◽  
Human Gastric Cancer

e15036 Background: Expression of the transcription factor FOXP3 is crucial for the regulatory T cells (Tregs) that engage in the maintenance of immunological self-tolerance and immune homeostasis. Recently, expression of FOXP3 in cancer cells and its association with prognosis have been shown in clinical studies. For gastric cancer, however, prognostic significance of the tumoral FOXP3 expression and its relationship with Tregs remains unknown. We observed the tumoral FOXP3 and Tregs from the 118 gastric cancer patients who underwent surgery to explore its relationships with the prognosis. Methods: Tissue samples from 118 cases of gastric cancer were used for the present study. We investigated the tumoral expression of FOXP3 and Tregs count in human gastric cancer tissue by the use of immunohistochemical analysis using a tissue microarray to explore the relation with clinicopathological variables by retrospective manner. Results: FOXP3-positive cancer cells were observed in 62 of 118 (52.5%) patients. Positive Tregs (Tregs≥10/HPF) were observed in 66 of 118 (55.9%) patients. There was significant positive relationship between positive Tregs count and the tumoral FOXP3 expression (P=0.006).Positive tumoral FOXP3 expression was significantly related with the better disease free survival but not with the overall survival. But increased Tregs count was significantly related with the better overall survival (P<0.01, P<0.01, respectively). When we divide the patients into four groups by the FOXP3 expression and the Tregs count, FOXP3/Tregs(+/+) group showed the best overall survival followed by FOXP3/Tregs(-/+) group, FOXP3/Tregs(+/-,) and FOXP3/Tregs(-/-), respectively. And the survival difference between the FOXP3/Tregs(+/+)-FOXP3/Tregs(-/+) group and the FOXP3/Tregs(+/-)-FOXP3/Tregs(-/-)group became more prominent by the Tregs count. Conclusions: These results suggest that positive tumoral FOXP3 expression in relation with the high Treg count is a new prognostic marker in gastric cancer. The combination of tumoral FOXP3 and Tregs enhanced its statistical power more than separated as a prognostic marker.

scholarly journals Asporin Expression on Stromal Cells and/or Cancer Cells Might Be A Useful Prognostic Marker in Patients with Diffuse-Type Gastric Cancer

2021 ◽  
pp. 1-8
Author(s):  
Masakazu Yashiro ◽  
Tsuyoshi Hasegawa ◽  
Yurie Yamamoto ◽  
Gen Tsujio ◽  
Sadaaki Nishimura ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Cancer Cells ◽  
Prognostic Marker ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Intestinal Type ◽  
Human Gastric Cancer ◽  
Diffuse Type ◽  
Diffuse Type Gastric Cancer

<b><i>Background:</i></b> Asporin (ASPN), a member of the proteoglycan family, has been shown to have a close correlation with cancer progression. It is not known whether ASPN is an oncogenic driver or a tumor suppressor in human gastric cancer. We sought herein to determine the relationship between ASPN expression and clinicopathological features of gastric cancer. <b><i>Patients and Methods:</i></b> A total of 296 gastric cancer patients (diffuse type, <i>n</i> = 144; intestinal type, <i>n</i> = 152) were enrolled. The ASPN expression level in each case was analyzed by immunohistochemistry. <b><i>Results:</i></b> ASPN was mainly found on stromal cells, especially on fibroblasts in tumor stroma, i.e., cancer-associated fibroblasts. The ASPN expression on either cancer cells or stromal cells was significantly high in macroscopic scirrhous-type tumors (<i>p</i> &#x3c; 0.001) and histologically abundant stroma-type tumors (<i>p</i> &#x3c; 0.001). Interestingly, a Kaplan-Meier survival curve of the 144 cases of diffuse-type gastric cancer revealed a significantly poorer prognosis in patients with ASPN-positive expression (<i>p</i> = 0.043; log rank) compared to those with ASPN-negative expression, but the prognoses were not significantly different in these subgroups of the 152 cases of intestinal-type gastric cancer. A multivariate analysis with respect to overall survival showed that ASPN expression on stromal cells and/or cancer cells was significantly correlated with overall survival in patients with diffuse-type gastric cancer (<i>p</i> = 0.041). <b><i>Conclusion:</i></b> In gastric cancer, ASPN was expressed mainly on stromal cells and partially on cancer cells. ASPN expression on stromal cells and/or cancer cells might be a useful prognostic marker in patients with diffuse-type gastric cancer.

High numbers of tumor-infiltrating FOXP3-positive regulatory T cells are associated with improved overall survival in follicular lymphoma

Blood ◽  
2006 ◽  
Vol 108 (9) ◽  
pp. 2957-2964 ◽  
Author(s):  
Joaquim Carreras ◽  
Armando Lopez-Guillermo ◽  
Bridget C. Fox ◽  
Lluis Colomo ◽  
Antonio Martinez ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cells ◽  
Regulatory T Cells ◽  
Follicular Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Significance ◽  
Prognostic Index ◽  
Specific Cell ◽  
First Relapse ◽  
The Impact

Abstract The tumor microenvironment plays an important role in the biologic behavior of follicular lymphoma (FL), but the specific cell subsets involved in this regulation are unknown. To determine the impact of FOXP3-positive regulatory T cells (Tregs) in the progression and outcome of FL patients, we examined samples from 97 patients at diagnosis and 37 at first relapse with an anti-FOXP3 monoclonal antibody. Tregs were quantified using computerized image analysis. The median overall survival (OS) of the series was 9.9 years, and the FL International Prognostic Index (FLIPI) was prognostically significant. The median Treg percentage at diagnosis was 10.5%. Overall, 49 patients had more than 10% Tregs, 30 between 5% to 10%, and 19 less than 5%, with a 5-year OS of 80%, 74%, and 50%, respectively (P = .001). Patients with very low numbers of Tregs (< 5%) presented more frequently with refractory disease (P = .007). The prognostic significance of Treg numbers was independent of the FLIPI. Seven transformed diffuse large B-cell lymphomas (DLBCLs) had lower Treg percentages (mean: 3.3%) than FL grades 1,2 (mean: 12.1%) or 3 (mean: 9%) (P < .02). In conclusion, high Treg numbers predict improved survival of FL patients, while a marked reduction in Tregs is observed on transformation to DLBCL.

scholarly journals Glycogen synthase kinase 3 beta inhibits microRNA-183-96-182 cluster via the β-Catenin/TCF/LEF-1 pathway in gastric cancer cells

2013 ◽  
Vol 42 (5) ◽  
pp. 2988-2998 ◽  
Author(s):  
Xiaoli Tang ◽  
Dong Zheng ◽  
Ping Hu ◽  
Zongyue Zeng ◽  
Ming Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Cancer Tissue ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
Cell Functions

Abstract Glycogen synthase kinase 3 beta (GSK3β) is a critical protein kinase that phosphorylates numerous proteins in cells and thereby impacts multiple pathways including the β-Catenin/TCF/LEF-1 pathway. MicroRNAs (miRs) are a class of noncoding small RNAs of ∼22 nucleotides in length. Both GSK3β and miR play myriad roles in cell functions including stem cell development, apoptosis, embryogenesis and tumorigenesis. Here we show that GSK3β inhibits the expression of miR-96, miR-182 and miR-183 through the β-Catenin/TCF/LEF-1 pathway. Knockout of GSK3β in mouse embryonic fibroblast cells increases expression of miR-96, miR-182 and miR-183, coinciding with increases in the protein level and nuclear translocation of β-Catenin. In addition, overexpression of β-Catenin enhances the expression of miR-96, miR-182 and miR-183 in human gastric cancer AGS cells. GSK3β protein levels are decreased in human gastric cancer tissue compared with surrounding normal gastric tissue, coinciding with increases of β-Catenin protein, miR-96, miR-182, miR-183 and primary miR-183-96-182 cluster (pri-miR-183). Furthermore, suppression of miR-183-96-182 cluster with miRCURY LNA miR inhibitors decreases the proliferation and migration of AGS cells. Knockdown of GSK3β with siRNA increases the proliferation of AGS cells. Mechanistically, we show that β-Catenin/TCF/LEF-1 binds to the promoter of miR-183-96-182 cluster gene and thereby activates the transcription of the cluster. In summary, our findings identify a novel role for GSK3β in the regulation of miR-183-96-182 biogenesis through β-Catenin/TCF/LEF-1 pathway in gastric cancer cells.

scholarly journals Ionizing radiation modulates the phenotype and function of human CD4+ induced regulatory T cells

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Samantha S. Beauford ◽  
Anita Kumari ◽  
Charlie Garnett-Benson
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Ionizing Radiation ◽  
Cancer Cells ◽  
Tumor Immunity ◽  
Foxp3 Expression ◽  
Cytotoxic T Cell ◽  
Suppressive Activity ◽  
Tgf Β1

Abstract Background The use of immunotherapy strategies for the treatment of advanced cancer is rapidly increasing. Most immunotherapies rely on induction of CD8+ tumor-specific cytotoxic T cells that are capable of directly killing cancer cells. Tumors, however, utilize a variety of mechanisms that can suppress anti-tumor immunity. CD4+ regulatory T cells can directly inhibit cytotoxic T cell activity and these cells can be recruited, or induced, by cancer cells allowing escape from immune attack. The use of ionizing radiation as a treatment for cancer has been shown to enhance anti-tumor immunity by several mechanisms including immunogenic tumor cell death and phenotypic modulation of tumor cells. Less is known about the impact of radiation directly on suppressive regulatory T cells. In this study we investigate the direct effect of radiation on human TREG viability, phenotype, and suppressive activity. Results Both natural and TGF-β1-induced CD4+ TREG cells exhibited increased resistance to radiation (10 Gy) as compared to CD4+ conventional T cells. Treatment, however, decreased Foxp3 expression in natural and induced TREG cells and the reduction was more robust in induced TREGS. Radiation also modulated the expression of signature iTREG molecules, inducing increased expression of LAG-3 and decreased expression of CD25 and CTLA-4. Despite the disconcordant modulation of suppressive molecules, irradiated iTREGS exhibited a reduced capacity to suppress the proliferation of CD8+ T cells. Conclusions Our findings demonstrate that while human TREG cells are more resistant to radiation-induced death, treatment causes downregulation of Foxp3 expression, as well as modulation in the expression of TREG signature molecules associated with suppressive activity. Functionally, irradiated TGF-β1-induced TREGS were less effective at inhibiting CD8+ T cell proliferation. These data suggest that doses of radiotherapy in the hypofractionated range could be utilized to effectively target and reduce TREG activity, particularly when used in combination with cancer immunotherapies.

Prognostic potential of FOXP3 expression in non-small cell lung cancer cells combined with tumor-infiltrating regulatory T cells

Lung Cancer ◽  
2012 ◽  
Vol 75 (1) ◽  
pp. 95-101 ◽  
Author(s):  
Hiroyuki Tao ◽  
Yusuke Mimura ◽  
Keisuke Aoe ◽  
Seiki Kobayashi ◽  
Hiromasa Yamamoto ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Foxp3 Expression ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Small Cell Lung

scholarly journals Prognostic Significance of ACP5 in Human Gastric Cancer

2020 ◽  
Author(s):  
Tailai An ◽  
Qian Liang ◽  
Tengfei Hao ◽  
Lingna Deng ◽  
Xiaofang Lu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cox Regression ◽  
Malignant Tumors ◽  
Prognostic Significance ◽  
Gastric Cancer Tissue ◽  
Expression Level ◽  
Cancer Tissue ◽  
Depth Of Invasion ◽  
Human Gastric Cancer ◽  
Cox Regression Analysis

Introduction: ACP5 plays crucial roles in multiple pathological processes, including the genesis and progression of malignant tumors. We performed this study with the purpose of determining whether ACP5 is a crucial biomarker significantly related with prognoses of gastric cancer (GC) patients. Methods: The expression level of ACP5 level was assessed among 170 gastric cancer specimens using immunohistochemistry (IHC). The associations between ACP5 expression and clinicopathological variables were evaluated. Univariate and multivariate Cox regression analyses were performed to confirm independent prognostic factors for GC patients. Results: It was revealed that ACP5 expression level in gastric cancer tissue was significantly associated with depth of invasion (P=0.029), and TNM stage (P=0.036). ACP5 was demonstrated by multivariate Cox regression analysis to be an independent prognostic factor for overall survival (OS) (P=0.001) and recurrence-free survival (RFS) (P=0.011) of GC patients. Conclusions: The expression of ACP5 in GC tissue was significantly higher than that in normal tissues and its overexpression was associated with a poorer prognosis, suggesting its potential roles in preventing and treating GC.

scholarly journals CCR7 Expression and Intratumoral FOXP3+ Regulatory T Cells are Correlated with Overall Survival and Lymph Node Metastasis in Gastric Cancer

PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. e74430 ◽  
Author(s):  
Shuang Zhou ◽  
Shuchang Xu ◽  
Huihong Tao ◽  
Zhiwei Zhen ◽  
Guolin Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
T Cells ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Regulatory T Cells ◽  
Ccr7 Expression ◽  
Node Metastasis
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