scholarly journals Immunosuppressive regulatory T cells are associated with aggressive breast cancer phenotypes: a potential therapeutic target

2008 ◽  
Vol 21 (12) ◽  
pp. 1527-1532 ◽  
Author(s):  
Sandra D Bohling ◽  
Kimberly H Allison
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Therapeutic Target ◽  
Potential Therapeutic Target ◽  
Cancer Phenotypes ◽  
Aggressive Breast Cancer

scholarly journals Fast and Efficient Genome Editing of Human FOXP3+ Regulatory T Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Lauren Van Zeebroeck ◽  
Rebeca Arroyo Hornero ◽  
Beatriz F. Côrte-Real ◽  
Ibrahim Hamad ◽  
Torsten B. Meissner ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Genome Editing ◽  
Therapeutic Target ◽  
Peripheral Tolerance ◽  
Immune Homeostasis ◽  
Cell Integrity ◽  
Potential Therapeutic Target ◽  
Functional Assays

FOXP3+ regulatory T cells (Tregs) are central for maintaining peripheral tolerance and immune homeostasis. Because of their immunosuppressive characteristics, Tregs are a potential therapeutic target in various diseases such as autoimmunity, transplantation and infectious diseases like COVID-19. Numerous studies are currently exploring the potential of adoptive Treg therapy in different disease settings and novel genome editing techniques like CRISPR/Cas will likely widen possibilities to strengthen its efficacy. However, robust and expeditious protocols for genome editing of human Tregs are limited. Here, we describe a rapid and effective protocol for reaching high genome editing efficiencies in human Tregs without compromising cell integrity, suitable for potential therapeutic applications. By deletion of IL2RA encoding for IL-2 receptor α-chain (CD25) in Tregs, we demonstrated the applicability of the method for downstream functional assays and highlighted the importance for CD25 for in vitro suppressive function of human Tregs. Moreover, deletion of IL6RA (CD126) in human Tregs elicits cytokine unresponsiveness and thus may prevent IL-6-mediated instability of Tregs, making it an attractive target to potentially boost functionality in settings of adoptive Treg therapies to contain overreaching inflammation or autoimmunity. Thus, our rapid and efficient protocol for genome editing in human Tregs may advance possibilities for Treg-based cellular therapies.

scholarly journals Immune‐checkpoint molecules on regulatory T‐cells as a potential therapeutic target in head and neck squamous cell cancers

2020 ◽  
Vol 111 (6) ◽  
pp. 1943-1957 ◽  
Author(s):  
Susumu Suzuki ◽  
Tetsuya Ogawa ◽  
Rui Sano ◽  
Taishi Takahara ◽  
Daisuke Inukai ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Therapeutic Target ◽  
Potential Therapeutic Target ◽  
Immune Checkpoint Molecules

Regulatory T cells in breast cancer as a potent anti-cancer therapeutic target

2020 ◽  
Vol 78 ◽  
pp. 106087 ◽  
Author(s):  
Vida Hashemi ◽  
Leili Aghebati Maleki ◽  
Maryam Esmaily ◽  
Ali Masjedi ◽  
Ghasem Ghalamfarsa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Therapeutic Target ◽  
Anti Cancer

scholarly journals O28: M6A DEMETHYLASE FTO A POTENTIAL TARGET IN BRAIN METASTATIC BREAST CANCER

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
S Keelan ◽  
S Charmsaz ◽  
S Purcell ◽  
D Varešlija ◽  
S Cocchiglia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Disease Progression ◽  
Therapeutic Target ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Potential Therapeutic Target ◽  
Rna Methylation ◽  
Pharmacological Inhibition

Abstract Introduction Brain metastasis (BrM) occurs in 10-30% of patients with advanced breast cancer (BC). BrM is increasing in incidence and confers a poor prognosis. We aimed to investigate the contribution of global epi-transcriptomic alterations in N6-methyladenosine (m6A) RNA-methylation as a therapeutic target in brain metastatic breast cancer. Method In preliminary studies we have demonstrated m6A demethylase – FTO as the main contributor to the progression of ER+ breast cancer. Furthermore an association between FTO and reduced disease-free-survival (n=870, p=0.018) was observed. Here we conducted an epigenetic inhibitor screen using two therapeutic agents, ethyl-ester-meclofenamic acid (MA2) and FB23-2 on matched 2D cell line, 3D organoid cultures and patient-derived xenografts (PDX) explant models of brain metastasis. Result Upon integration of mapped global RNA methylation landscape with matched proteomic analysis, we observed genome-wide RNA hypo-methylation of key pluripotency genes, including SOX2 and KLF4, as key players underlying tumour progression to the brain.  Genetic and pharmacological inhibition of FTO in novel ex vivo models of BrM significantly reduced protein expression levels of KLF4 and SOX2. Moreover, pharmacological inhibition of FTO with MA2 and FB23-2, inhibited cell proliferation in endocrine-resistant BC and patient BrM cells. We translate our findings to the clinic by demonstrating the efficacy of anti-FTO therapies in several unique PDX and 3D organoid BrM models. Conclusion Our results reveal epi-transcriptional remodelling events as a key mechanism in BrM. This study establishes an early role for targeting RNA methylation in the management of disease progression and presents FTO as a potential therapeutic target in BrM. Take-home message This study establishes an early role for targeting RNA methylation in the management of disease progression and presents FTO as a potential therapeutic target in brain metastatic breast cancer.

scholarly journals Tumor specific regulatory T cells in the bone marrow of breast cancer patients selectively upregulate the emigration receptor S1P1

2017 ◽  
Vol 66 (5) ◽  
pp. 593-603 ◽  
Author(s):  
Anchana Rathinasamy ◽  
Christoph Domschke ◽  
Yingzi Ge ◽  
Hans-Henning Böhm ◽  
Steffen Dettling ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
T Cells ◽  
Regulatory T Cells ◽  
Cancer Patients ◽  
Breast Cancer Patients
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