Search results for "FoxP3"
showing 10 items of 140 documents
OX40 expression in tumor-associated Tregs as a potential prognostic biomarker and immunotherapeutic target in ovarian cancer.
2015
e16576 Background: Treatment of ovarian cancer (OC) remains very challenging, with 80-85% of the cases still dying after relapse to standard chemotherapy, and novel treatments are urgently needed. Expansion of regulatory T cells (Tregs) is considered the major factor limiting immune responses to OC. Agonist antibodies against the co-stimulatory receptor OX40 have recently demonstrated to abrogate Treg functions and are under clinical evaluation. We thus studied whether OX40 constituted a valid target of OC-associated Tregs. Methods: Treg immunophenotypic analyses were performed by flow cytometry in ascites and OC specimens and studied in association with patients’ outcome Results: CD4+CD25+…
Analysis of the prognostic impact of Treg-related genes in tumor and stroma in resectable NSCLC
2013
11073 Background: Immunosuppressive regulatory T lymphocytes (Tregs) have been proved to play a critical role in immune tolerance to tumor. In this study we have analyzed the expression of 11 genes related to Tregs in both tumor and stroma samples of resectable NSCLC patients. Methods: Primary tumor tissues of FFPE samples from 125 early-stage NSCLC patients were used in this retrospective study. The most representative areas of tumor cells and tumor stroma of each sample were carefully micro-dissected. RTqPCR using hydrolysis probes (TaqMan, Applied Biosystems) was performed to assess the expression of Treg markers such as: CD127, CD25, FOXP3, CTLA-4, IL-10, TGFB-1, LAG-3, GITR and TNF-a …
Human FOXP3 and cancer.
2010
FOXP3 is a transcription factor necessary and sufficient for induction of the immunosuppressive functions in regulatory T lymphocytes. Its expression was first considered as specific of this cell type, but FOXP3 can also be transiently expressed in T-cell antigen receptor-activated human nonregulatory T cells. Recent data indicate that FOXP3 is also expressed by some nonlymphoid cells, in which it can repress various oncogenes that are restored following FOXP3 deletion or mutation. This review summarizes major advances in (1) the understanding of Foxp3 functions in human regulatory T cells, (2) the prognostic significance of Foxp3-expressing T cells in human malignancies and (3) the signifi…
Abstract 1847: Anti-GARP antibody DS-1055a augments antitumor immunity by depleting highly suppressive GARP+ regulatory T cells
2021
Abstract Immune checkpoint blockers (ICBs) have drastically changed the clinical care of cancer; however, the population of patients who can benefit is relatively small because of intrinsic or acquired resistance to immune therapy. To evade immune destruction, tumors exploit several distinct strategies including immunosuppressive cells such as regulatory T (Treg) cells. Treg cells, an essential component for maintaining self-tolerance, inhibit antitumor immunity, consequently hindering protective cancer immunosurveillance and hampering effective antitumor immune responses in tumor-bearing hosts. It is often reported that a high ratio of Treg cells to effector CD8+ T cells is associated with…
Abstract B157: OX40 expression in tumor-associated Tregs as a potential prognostic biomarker and immunotherapeutic target in ovarian cancer
2016
Abstract Background - Treatment of ovarian cancer remains very challenging, with 80-85% of the cases still dying after relapse to standard chemotherapy, and alternative treatments are urgently needed. Expansion of regulatory T cells (Tregs) is considered the major factor limiting spontaneous immune responses to ovarian cancer. Agonist antibodies against the co-stimulatory receptor OX40 have recently demonstrated to abrogate Treg functions and are under clinical evaluation. We thus studied whether OX40 constituted a valid target of ovarian cancer-associated Tregs. Methods -Treg immunophenotypic analyses were performed by flow cytometry in ascites and ovarian cancer specimens and studied in a…
Allogeneic effector/memory Th-1 cells impair FoxP3+ regulatory T lymphocytes and synergize with chaperone-rich cell lysate vaccine to treat leukemia
2011
AbstractTherapeutic strategies combining the induction of effective antitumor immunity with the inhibition of the mechanisms of tumor-induced immunosuppression represent a key objective in cancer immunotherapy. Herein we demonstrate that effector/memory CD4+ T helper-1 (Th-1) lymphocytes, in addition to polarizing type-1 antitumor immune responses, impair tumor-induced CD4+CD25+FoxP3+ regulatory T lymphocyte (Treg) immunosuppressive function in vitro and in vivo. Th-1 cells also inhibit the generation of FoxP3+ Tregs from naive CD4+CD25−FoxP3− T cells by an interferon-γ–dependent mechanism. In addition, in an aggressive mouse leukemia model (12B1), Th-1 lymphocytes act synergistically with …
Intrinsic TNFR2 signaling in T regulatory cells provides protection in CNS autoimmunity
2018
Significance In spite of TNF involvement in the pathogenesis of multiple sclerosis (MS), systemic TNF neutralization in MS patients was not successful. One of the possible reasons is that TNF possesses both pathogenic and protective features that may be related to TNFR1 versus TNFR2 receptor engagement. This study uncovers one of such protective functions of TNF mediated by intrinsic TNFR2 signaling in Treg cells. In mice bearing humanized TNF and TNFR2 genetic loci, TNFR2 ablation restricted to Treg cells led to reduced capacity to control Th17 cell responses, exacerbated experimental autoimmune encephalomyelitis (EAE) development, and affected the maintenance of Treg cells. These findings…
P33 Up-regulation of FOXP3 T regulatory lymphocytes in patients with high-grade squamous intraepithelial lesions correlated with HPV infection
2019
Introduction/Background Regulatory (FOXP3+) T cells (Tregs) comprise a subpopulation of CD4+ T cells that suppress autoreactive immune cells, thereby protecting organs and tissues from autoimmunity. Novel therapeutic strategies for cervical cancer and squamous intraepithelial lesions (SIL) focus on immune-modulatory and cancer vaccination approaches. The aim of this study was to analyze the role of T regulatory cells (Tregs), CD4 and CD8 T lymphocytes and HPV status in low and high grade squamous intraepithelial lesions (LSIL and HSIL). Methodology 62 patients were enrolled in the study in Riga East University Hospital. Each patient had undergone a biopsy or electroexcision of the cervix. T…
Dependence on nuclear factor of activated T-cells (NFAT) levels discriminates conventional T cells from Foxp3 + regulatory T cells
2012
Several lines of evidence suggest nuclear factor of activated T-cells (NFAT) to control regulatory T cells: thymus-derived naturally occurring regulatory T cells (nTreg) depend on calcium signals, the Foxp3 gene harbors several NFAT binding sites, and the Foxp3 (Fork head box P3) protein interacts with NFAT. Therefore, we investigated the impact of NFAT on Foxp3 expression. Indeed, the generation of peripherally induced Treg (iTreg) by TGF-β was highly dependent on NFAT expression because the ability of CD4 + T cells to differentiate into iTreg diminished markedly with the number of NFAT family members missing. It can be concluded that the expression of Foxp3 in TGF-β–induced iTreg depends…
TGF-β Dependent T-Cell Regulation in Colitis and Colon Cancer
2008
Transforming growth factor-β (TGF-β) is a potent growth inhibitor endowed with tumor-suppressing activity. Unfortunately, cancers are often resistant to such growth inhibition. This evasion frequently results from a genetic loss of functional TGF-β signaling components. On the other hand, cancer cells often produce high amounts TGF-β1 by themselves and sometimes respond to it with invasion and metastasis. Much effort is being done to develop therapeutic approaches to modulate TGF-β signaling in cancer cells either to inhibit the TGF-β-induced invasive phenotype or to reestablish its growth-inhibitory activities. However, TGF-β is a pleiotropic cytokine with important functions not only in c…