Cancer Deaths in UK Plummet in Middle-aged People March 13, 2024
Introduction:
(Eurekalert)
• A first of its kind study by Cancer Research UK reveals premature cancer death rates in 35–69-year-olds fell by more than a third over 25 years
• Improvements in the UK are a result of smokefree policies, prevention measures, early detection programmes like cancer screening, and more effective treatment options
• But the study paints a mixed picture with cancer cases on the rise and cancer mortality rates still too high
• The charity’s manifesto, ‘Longer, better lives’ outlines action the UK Government can take to save 20,000 lives from cancer every year by 2040
Making a personalized T cell therapy for cancer patients currently takes at least six months; scientists at the German Cancer Research Center (DKFZ) and the University Medical Center Mannheim have shown that the laborious first step of identifying tumor-reactive T cell receptors for patients can be replaced with a machine learning classifier that halves this time.
Personalized cellular immunotherapies are considered promising new treatment options for various types of cancer. One of the therapeutic approaches currently being tested is so-called "T-cell receptor transgenic T-cells." The idea behind this is that immune T cells from a patient are equipped in the laboratory to recognize the patient's own unique tumor and then reinfused in large numbers to effectively kill the tumor cells.
The MYCN oncoprotein (proteins related to the growth of cancer cells) plays a key role in starting, advancing and making it difficult to treat various human cancers. When MYCN is overactive, especially in high-risk neuroblastoma (childhood cancer often found in the adrenal glands), the tumors become less responsive to immunotherapy—a treatment that uses the body's immune system to fight cancer. Still, recognition of this problem has not led to any effective strategies to tackle this problem.
In a new study from Boston University Chobanian & Avedisian School of Medicine, researchers found that MYCN selectively increases the levels of a signaling molecule, CKLF, in neuroblastoma cells to suppress anti-tumor immune responses and promote tumor aggressiveness. The findings appear online in Science Advances.
Researchers Gain Insight into Why T Cells Lose Energy in Solid Tumors by Jessica Thaxton
March 15, 2024
Introduction:
(UNC Health) New research by the lab of Jessica Thaxton, PhD, MsCR, in the Department of Cell Biology and Physiology at the UNC School of Medicine and colleagues in the Immunotherapy Group at Lineberger Comprehensive Cancer Center, has unveiled new clues behind T-cell metabolism, that could enhance immunotherapies that rely on T cells to fight cancer.
T cells are often called “assassins” or “killers” because they can orchestrate and carry out missions to hunt down bacteria, viruses, and cancer cells throughout the body. Mighty as they may be, recent research has shown that once T cells infiltrate the environment of a solid tumor, they lose the energy needed to combat the cancer.
A research team led by Jessica Thaxton, PhD, MsCR, associate professor of cell biology and physiology and co-leader of the Cancer Cell Biology Program at the UNC Lineberger Comprehensive Cancer Center, aimed to understand why T cells do not sustain energy in tumors.
Using their expertise in tumor immunity and metabolism, the Thaxton Lab, led by the Katie Hurst, MPH, and 4th year graduate student Ellie Hunt, found that a metabolic enzyme called Acetyl-CoA Carboxylase (ACC) causes T cells to store fat rather than burning fat for energy.
“Our discovery fills a long-standing gap in knowledge regarding why T cells in solid tumors don’t appropriately generate energy,” said Thaxton. “We inhibited the expression of ACC in mouse cancer models, and we observed that T cells were able to persist much better in solid tumors.”
Researchers at the University of Toronto's Donnelly Centre for Cellular and Biomolecular Research have found two enzymes that work against the chemotherapy drug gemcitabine, preventing it from effectively treating pancreatic cancer.
The enzymes—APOBEC3C and APOBEC3D—increase during gemcitabine treatment and promote resistance to DNA replication stress in pancreatic cancer cells.
This, in turn, counteracts the effects of gemcitabine and allows for the growth of cancer cells.
"Pancreatic cancer has proven to be very challenging to treat, as it is usually diagnosed at stage 3 or 4," said Tajinder Ubhi, first author on the study and a former Ph.D. student in biochemistry in U of T's Temerty Faculty of Medicine.
Monitoring levels of DNA shed by tumors and circulating in the bloodstream could help doctors accurately assess how gastroesophageal cancers are responding to treatment, and potentially predict future prognosis, suggests a new study led by researchers at the Johns Hopkins Kimmel Cancer Center and its Bloomberg–Kimmel Institute for Cancer Immunotherapy.
The study tracked minimal residual disease (the amount of cancer left following treatment) by analyzing circulating tumor DNA (ctDNA), showing how these "liquid biopsies" can provide valuable insights into treatment outcomes over time. Absence of ctDNA was seen occurring together with specific activation of T cells that are part of the immune system's defense to recognize and fight cancer.
A collaboration between scientists from St. Jude Children's Research Hospital and Dana-Farber Cancer Institute uncovered four proteins that govern the identity of anaplastic large cell lymphoma (ALCL), an aggressive form of cancer. These proteins comprise a core regulatory circuit (CRC) that surprisingly incorporates a dysregulated signaling protein.
Establishing the CRC for this lymphoma gives researchers insight into potential vulnerabilities that may be future therapeutic targets. The findings were published in Cell Reports Medicine.
"Mutations in signaling pathways have long been known to drive oncogenic transformation and tumor progression," said senior co-corresponding author Mark Zimmerman, Ph.D., currently of Foghorn Therapeutics, previously of Dana-Farber Cancer Institute and Boston Children's Hospital.
Thanks to an unusual application of game theory and machine learning technology, a large team of scientists led by experts at Cincinnati Children's has published the world's most detailed "atlas" of the many types of stem cells and early progenitors involved in producing human blood from diverse donors.
The team has identified more than 80 distinct subsets of hematopoietic stem and progenitor cells (HSPCs)—early-stage cells that kick off production of mature red cells, white cells and other elements of our complex blood system. Details were published in Nature Immunology.
"We believe our highly focused capture strategy of the earliest HSPCs, intermediate cell states plus stromal populations, and the most abundant end states provides the deepest view of bone marrow stem and progenitor compartments described to date," the co-authors state.
The study was led by co-first authors Xuan Zhang, Ph.D., and Baobao Song, Ph.D., and co-corresponding authors Nathan Salomonis, Ph.D., and H. Leighton Grimes, Ph.D., all researchers with Cincinnati Children's. Overall, the study includes 26 co-authors from four academic medical centers and two biotech companies.
