Glucagon-like peptide 1 receptor is a T cell-negative costimulatory molecule

Role of GLP-1R in T Cells and Its Regulatory Mechanism for Anti-transplant Immunity and Anti-tumor Immunity Academic Background Glucagon-like peptide-1 receptor (GLP-1R) is known as a key regulator of glucose metabolism, primarily expressed in pancreatic β cells. Previous studies have clarified that GLP-1R agonists have significant effects in reduc...

QDPR Deficiency Drives Immune Suppression in Pancreatic Cancer

Background Pancreatic Ductal Adenocarcinoma (PDAC) is a malignancy with a highly immunosuppressive tumor microenvironment (TME), showing strong resistance to immune checkpoint blockade (ICB) therapies, such as anti-PD-1 and anti-CTLA-4 treatments. Myeloid-Derived Suppressor Cells (MDSCs) derived from tumors play a critical role in tumor immune supp...

Acetyl-CoA Carboxylase Obstructs CD8+ T Cell Lipid Utilization in the Tumor Microenvironment

Inhibition of Acetyl-CoA Carboxylase Enhances Antitumor Immunity of Tumor-Infiltrating CD8+ T Cells Background and Objective In recent years, the impact of metabolic changes in the Tumor Microenvironment (TME) on the function of Tumor-Infiltrating Lymphocytes (TILs) has become a hot topic in immunological research. Although T cells possess strong a...

Glycometabolic Reprogramming-Induced XRCC1 Lactylation Confers Therapeutic Resistance in ALDH1A3-Overexpressing Glioblastoma

Background Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults, characterized by high recurrence and mortality rates. Despite active chemotherapy and radiotherapy post-surgery, GBM remains insensitive to existing treatment regimens, and patients usually have a poor prognosis. Recent studies indicate that the...

PKD1 mutant clones within cirrhotic livers inhibit steatohepatitis without promoting cancer

Background This paper aims to explore the function of somatic PKD1 mutations in cirrhosis and their impact on liver health without inducing cancer. The authors conducted this research because, although somatic mutations accumulate in non-malignant tissues and increase with age, it remains unclear whether these mutant clones are beneficial for organ...

TH17 Cell-Intrinsic Glutathione/Mitochondrial-IL-22 Axis Protects Against Intestinal Inflammation

Intrinsic Glutathione/Mitochondrial-IL-22 Axis in TH17 Cells and Its Protective Mechanism Against Intestinal Inflammation Background Introduction A large amount of reactive oxygen species (ROS) is generated in the intestine, and the role of T-cell antioxidant mechanisms in maintaining intestinal homeostasis remains unclear. This paper studies the i...

Reactive Oxygen Species Regulation by NCF1 Governs Ferroptosis Susceptibility of Kupffer Cells to MASH

NCF1 Regulates Reactive Oxygen Species Vulnerability to Ferroptosis in Kupffer Cells and Its Impact on MASH Introduction Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), has a global prevalence of up to 25.2% and is a leading cause of chronic liver disease in adults and c...

Short-Term Cold Exposure Induces Persistent Epigenomic Memory in Brown Fat

Short-term Cold Exposure Induces Persistent Epigenomic Memory in Brown Adipose Tissue Background Brown Adipose Tissue (BAT) is the primary non-shivering thermogenic organ in mammals that dissipates chemical energy as heat under cold stimuli. BAT is characterized by a high density of mitochondria containing Uncoupling Protein 1 (UCP1), which generat...

Intermittent clearance of p21-highly-expressing cells extends lifespan and confers sustained benefits to health and physical function

Intermittent Clearance of High p21-Expressing Cells Extends Lifespan and Delivers Sustained Health Benefits Research Background With the significant extension of human lifespan, the global elderly population is rapidly increasing. Elderly individuals often face decreased functionality and various chronic diseases in their later years, such as cardi...

Nicotinamide Metabolism Face-off Between Macrophages and Fibroblasts Manipulates the Microenvironment in Gastric Cancer

Macroscopic and Microscopic Mechanisms of Nicotinamide Metabolism Antagonism: Manipulation of the Gastric Cancer Microenvironment Background Introduction Gastric cancer (GC) is a type of cancer characterized by a unique and heterogeneous tumor microenvironment (TME). Despite advances in immune checkpoint blockade (ICB) therapy for gastric cancer, n...