PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Oncotarget: Genome wide DNA methylation landscape reveals glioblastoma's influence

These Oncotarget results suggest that GBM might induce epigenetic alterations in tumor infiltrating CD4 T-cells

Oncotarget: Genome wide DNA methylation landscape reveals glioblastoma's influence
2021-07-05
(Press-News.org) Oncotarget published "Genome wide DNA methylation landscape reveals glioblastoma's influence on epigenetic changes in tumor infiltrating CD4+ T cells" which reported that whole-genome bisulfite sequencing of tumor infiltrating and blood CD4 T-cell from GBM patients showed 13571 differentially methylated regions and a distinct methylation pattern of methylation of tumor infiltrating CD4 T-cells with significant inter-patient variability.

The methylation changes also resulted in transcriptomic changes with 341 differentially expressed genes in CD4 tumor infiltrating T-cells compared to blood.

Analysis of specific genes involved in CD4 differentiation and function revealed differential methylation status of TBX21, GATA3, RORC, FOXP3, IL10 and IFNG in tumor CD4 T-cells.

Interestingly, the authors observed dysregulation of several ligands of T cell function genes in GBM tissue corresponding to the T-cell receptors that were dysregulated in tumor infiltrating CD4 T-cells.

These Oncotarget results suggest that GBM might induce epigenetic alterations in tumor infiltrating CD4 T-cells there by influencing anti-tumor immune response by manipulating differentiation and function of tumor infiltrating CD4 T-cells.

These Oncotarget results suggest that GBM might induce epigenetic alterations in tumor infiltrating CD4 T-cells

Dr. Mahua Dey from The University of Wisconsin-Madison as well as The Indiana University School of Medicine said, "Naïve CD4+ helper T cell population is known for its polyfunctionality and highly plastic characteristics."

In the tumor microenvironment, lineage commitments of CD4 T cells reflect initiation of new programs of gene expression within tumor infiltrating naïve T cells.

The GBM tumor microenvironment is known to be extremely immunosuppressive, possessing multiple unique properties including:

Impaired cellular immunity no dearth of tumor infiltrating T cells High levels of TGFβ secreted by resident as well as circulating microglia and Expression of several inhibitory ligands, eliciting anergy and apoptosis of cytotoxic lymphocytes in the TME, immune checkpoints expression, and increased infiltration of immunosuppressive cells. Genome wide methylation sequencing showed 13571 uniquely differentially methylated regions , mostly concentrated around the TSS, in the CD4 T cells from GBM patient tumor compared to blood.

Furthermore, combining transcriptomic data from RNAseq analysis with DNA methylation, we observed differential methylation of gene sets specific for CD4 T cells including Th1, Th2, Th17 and iTregs in GBM tumors, although with significant interpatient variability.

In conclusion, this data for the first time, report unique DNA methylation pattern and gene expression profiles in GBM associated tumor infiltrating CD4 T cells compared to CD4 T-cell from the blood of the same patient and some of their ligands on the GBM cells suggesting that CD4 T cells function and differentiation may be influenced by the GBM TME by way of epigenetic mechanisms such as, DNA methylation.

The Dey Research Team concluded in their Oncotarget Research Output, "in the present clinical corelative report, we demonstrated that differential DNA methylation pattern might influence gene expression in tumor infiltering CD4+ T cells as compared to circulating blood CD4+ T cells in GBM patients. Our findings provide evidence that GBM might be influencing the state of tumor infiltrating CD4+ T cells by epigenetic modification in the form of DNA methylation of key immune function regulating genes and influencing the fate of helper T cells in the GBM TME. Based on our observations we believe that perhaps epigenetic interaction between GBM and tumor infiltrating CD4+ T cells is responsible for the immunosuppressed state seen in the GBM patients. Our data convincingly show that there is significant inter-patient variability in the GBM tumor ligand expression of various T-cell modulating ligands and consequently striking differences in the methylation pattern and gene expression in tumor infiltrating CD4+ T-cells. This has a very strong implication for selecting future patients for immunotherapy trials who will have better likelihood of responding to immunotherapy than others based on their tumor immune signature. The findings from our corelative study needs to be further validated in the experimental setting."

INFORMATION:

DOI - https://doi.org/10.18632/oncotarget.27955

Full text - https://www.oncotarget.com/article/27955/text/

Correspondence to - Mahua Dey - dey@neurosurgery.wisc.edu

Keywords - glioblastoma, malignant glioma, CD4+ T cell, DNA methylation, brain cancer

About Oncotarget

Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:

SoundCloud - https://soundcloud.com/oncotarget
Facebook - https://www.facebook.com/Oncotarget/
Twitter - https://twitter.com/oncotarget
LinkedIn - https://www.linkedin.com/company/oncotarget
Pinterest - https://www.pinterest.com/oncotarget/
Reddit - https://www.reddit.com/user/Oncotarget/

Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls


[Attachments] See images for this press release:
Oncotarget: Genome wide DNA methylation landscape reveals glioblastoma's influence

ELSE PRESS RELEASES FROM THIS DATE:

Lower exposure to UVB light may increase colorectal cancer risk

2021-07-05
Inadequate exposure to UVB light from the sun may be associated with an increased risk of colorectal cancer, particularly in older age groups, according to a study using data on 186 countries, published in the open access journal BMC Public Health. Researchers at the University of California San Diego, USA investigated possible associations between global levels of UVB light in 2017 and rates of colorectal cancer for different countries and age groups in 2018. The authors found that lower UVB exposure was significantly correlated with higher rates of colorectal cancer across all ...

Goldfinder: scientists discover why we can find gold at all

Goldfinder: scientists discover why we can find gold at all
2021-07-05
Why are gold deposits found at all? Gold is famously unreactive, and there seems to be little reason why gold should be concentrated, rather than uniformly scattered throughout the Earth's crust. Now an international group of geochemists have discovered why gold is concentrated alongside arsenic, explaining the formation of most gold deposits. This may also explain why many gold miners and others have been at risk from arsenic poisoning. This work is presented at the Goldschmidt conference, after recent publication*. Gold has been prized for millennia, for its purity and stability. It's also rare enough to retain its value - the World Gold Council estimates that all the gold ever mined in the world would fit into a 20x20x20-meter cube. It is valued for its beauty, but also because it ...

Scientists reconstruct Mediterranean silver trade, from Trojan War to Roman Republic

Scientists reconstruct Mediterranean silver trade, from Trojan War to Roman Republic
2021-07-05
Scientists have reconstructed the Eastern Mediterranean silver trade, over a period including the traditional dates of the Trojan War, the founding of Rome, and the destruction of Solomon's Temple in Jerusalem. The team of French, Israeli and Australian scientists and numismatists found geochemical evidence for pre-coinage silver trade continuing throughout the Mediterranean during the Late Bronze and Iron Age periods, with the supply slowing only occasionally. Silver was sourced from the whole north-eastern Mediterranean, and as far away as the Iberian ...

The City of David and the sharks' teeth mystery

The City of David and the sharks teeth mystery
2021-07-04
Scientists have found an unexplained cache of fossilised shark teeth in an area where there should be none - in a 2900 year old site in the City of David in Jerusalem. This is at least 80 km from where these fossils would be expected to be found. There is no conclusive proof of why the cache was assembled, but it may be that the 80 million-year-old teeth were part of a collection, dating from just after the death of King Solomon*. The same team has now unearthed similar unexplained finds in other parts of ancient Judea. Presenting the work at the Goldschmidt Conference, lead researcher, Dr. Thomas Tuetken (University of Mainz, Institute of Geosciences) said: "These fossils are not in their original setting, so they have been moved. They were probably valuable to someone; ...

Stress-free path to stress-free metallic films paves the way for next-gen circuitry

Stress-free path to stress-free metallic films paves the way for next-gen circuitry
2021-07-03
Tokyo, Japan - Researchers from Tokyo Metropolitan University have used high power impulse magnetron scattering (HiPIMS) to create thin films of tungsten with unprecedentedly low levels of film stress. By optimizing the timing of a "substrate bias pulse" with microsecond precision, they minimized impurities and defects to form crystalline films with stresses as low as 0.03 GPa, similar to those achieved through annealing. Their work promises efficient pathways for creating metallic films for the electronics industry. Modern electronics relies on the intricate, nanoscale deposition of thin metallic films onto surfaces. This is easier said than done; unless done right, "film stresses" arising from the microscopic internal structure of the film ...

Cancer: Immunotherapies without side effects?

Cancer: Immunotherapies without side effects?
2021-07-02
In recent years, immunotherapy has revolutionised the field of cancer treatment. However, inflammatory reactions in healthy tissues frequently trigger side effects that can be serious and lead to the permanent discontinuation of treatment. This toxicity is still poorly understood and is a major obstacle to the use of immunotherapy. Scientists from the University of Geneva (UNIGE), Switzerland, and Harvard Medical School, United States, have succeeded in establishing the differences between deleterious immune reactions and those targeting tumour cells that are sought after. It appears that while the immune mechanisms are similar, the cell ...

Cancer cells eat themselves to survive

2021-07-02
It is the membrane of cancer cells that is at the focus of the new research now showing a completely new way in which cancer cells can repair the damage that can otherwise kill them. In both normal cells and cancer cells, the cell membrane acts as the skin of the cells. And damage to the membrane can be life threatening. The interior of cells is fluid, and if a hole is made in the membrane, the cell simply floats out and dies - a bit like a hole in a water balloon. Therefore, damage to the cell membrane must be repaired quickly, and now research from a team of Danish researchers shows that cancer cells use a ...

NYUAD study maps nanobody structure, leading to new ways to potentially fight diseases

2021-07-02
Fast facts: Nanobodies have been shown to inhibit the dysfunction of key proteins involved with various diseases such as rheumatoid arthritis, osteoarthritis, psoriasis, B-cell lymphoma, and breast cancer Understanding the structure of a nanobody helps to better understand its disease-fighting potential Typically, the protein structure is determined from solid samples. Researchers at NYUAD used a liquid state technique to determine protein structure. Abu Dhabi, UAE: For the first time in the UAE, researchers at NYU Abu Dhabi have used ...

Unusual currents explain mysterious red crab strandings

Unusual currents explain mysterious red crab strandings
2021-07-02
For decades, people have wondered why pelagic red crabs--also called tuna crabs--sometimes wash ashore in the millions on the West Coast of the United States. New research shows that atypical currents, rather than abnormal temperatures, likely bring them up from their home range off Baja California. Alongside the discovery, the scientists also created a seawater flow index that could help researchers and managers detect abnormal current years. The new study, published July 1 in Limnology and Oceanography, began after lead author Megan Cimino biked past a pelagic red crab stranding on her way to her office in Monterey ...

More than half of wheelchair users with spinal cord injury needed repairs in past 6 months

More than half of wheelchair users with spinal cord injury needed repairs in past 6 months
2021-07-02
East Hanover, NJ. July 2, 2021. Among wheelchair users with spinal cord injury 42 percent reported adverse consequences related to needing wheelchair repair, according to a team of experts in spinal cord injury rehabilitation. The research team, comprised of investigators from the Spinal Cord Injury Model System, determined that this ongoing problem requires action such as higher standards of wheelchair performance, access to faster repair service, and enhanced user training on wheelchair maintenance and repair. The article, "Factors Influencing Incidence of Wheelchair Repairs and Consequences Among Individuals with Spinal Cord Injury" (doi: 10.1016/j.apmr.2021.01.094) was published online in ...

LAST 30 PRESS RELEASES:

Social fish with low status are so stressed out it impacts their brains

Predicting the weather: New meteorology estimation method aids building efficiency

Inside the ‘swat team’ – how insects react to virtual reality gaming 

Oil spill still contaminating sensitive Mauritius mangroves three years on

Unmasking the voices of experience in healthcare studies

Pandemic raised food, housing insecurity in Oregon despite surge in spending

OU College of Medicine professor earns prestigious pancreatology award

Sub-Saharan Africa leads global HIV decline: Progress made but UNAIDS 2030 goals hang in balance, new IHME study finds

Popular diabetes and obesity drugs also protect kidneys, study shows

Stevens INI receives funding to expand research on the neural underpinnings of bipolar disorder

Protecting nature can safeguard cities from floods

NCSA receives honors in 2024 HPCwire Readers’ and Editors’ Choice Awards

Warning: Don’t miss Thanksgiving dinner, it’s more meaningful than you think

Expanding HPV vaccination to all adults aged 27-45 years unlikely to be cost-effective or efficient for HPV-related cancer prevention

Trauma care and mental health interventions training help family physicians prepare for times of war

Adapted nominal group technique effectively builds consensus on health care priorities for older adults

Single-visit first-trimester care with point-of-care ultrasound cuts emergency visits by 81% for non-miscarrying patients

Study reveals impact of trauma on health care professionals in Israel following 2023 terror attack

Primary care settings face barriers to screening for early detection of cognitive impairment

November/December Annals of Family Medicine Tip Sheet

Antibiotics initiated for suspected community-acquired pneumonia even when chest radiography results are negative

COVID-19 stay-at-home order increased reporting of food, housing, and other health-related social needs in Oregon

UW-led research links wildfire smoke exposure with increased dementia risk

Most U.S. adults surveyed trust store-bought turkey is free of contaminants, despite research finding fecal bacteria in ground turkey

New therapy from UI Health offers FDA-approved treatment option for brittle type 1 diabetes

Alzheimer's: A new strategy to prevent neurodegeneration

A clue to what lies beneath the bland surfaces of Uranus and Neptune

Researchers uncover what makes large numbers of “squishy” grains start flowing

Scientists uncover new mechanism in bacterial DNA enzyme opening pathways for antibiotic development

New study reveals the explosive secret of the squirting cucumber

[Press-News.org] Oncotarget: Genome wide DNA methylation landscape reveals glioblastoma's influence
These Oncotarget results suggest that GBM might induce epigenetic alterations in tumor infiltrating CD4 T-cells