Tumor Extracellular Vesicle–Derived PD-L1 Promotes T Cell Senescence Through Lipid Metabolism Reprogramming

PD-L1 in Tumor-Derived Extracellular Vesicles Promotes T Cell Senescence through Lipid Metabolism Reprogramming Academic Background In recent years, immunotherapy has shown great promise in cancer treatment, particularly in checkpoint blockade therapies targeting PD-1/PD-L1 (programmed cell death protein 1 and its ligand) and CTLA-4 (cytotoxic T-ly...

In Vivo Expansion of Gene-Targeted Hepatocytes through Transient Inhibition of an Essential Gene

Breakthrough in Gene Therapy: Repair Drive Technology Enables In Vivo Expansion of Hepatocytes Academic Background Gene therapy has become a hot topic in medical research in recent years, especially for liver diseases. Due to the central role of the liver in metabolism, it has become a critical target for research. Although existing gene-editing te...

Coactivation of Innate Immune Suppressive Cells Induces Acquired Resistance Against Combined TLR Agonism and PD-1 Blockade

Mechanism of Combined Immune Checkpoint Blockade Therapy Academic Background Immune Checkpoint Blockade (ICB) is a revolutionary cancer treatment aimed at reactivating effector T cells to combat cancer. However, more than half of patients do not respond to ICB, especially those with immunologically “cold” tumors (tumors with fewer immune cells in t...

Organ-Specific Microenvironments Drive Divergent T Cell Evolution in Acute Graft-Versus-Host Disease

Study on Organ-Specific T Cell Differentiation in Acute Graft-Versus-Host Disease (AGVHD) Academic Background Acute Graft-Versus-Host Disease (AGVHD) is a common and severe complication following Allogeneic Hematopoietic Stem Cell Transplantation (HCT), caused by the immune attack of donor T cells on host tissues. Although the pathological mechanis...

Triple Knockdown of CD11a, CD49d, and PSGL1 in T Cells Reduces CAR-T Cell Toxicity but Preserves Activity Against Solid Tumors in Mice

Study on Reducing Toxicity of CAR-T Cell Therapy for Solid Tumors Academic Background Chimeric antigen receptor T-cell (CAR-T) therapy has made significant progress in treating hematologic malignancies, but its application in solid tumors faces major challenges. Solid tumors often lack tumor-specific antigens (TSAs), and CAR-T cells may attack norm...

Ciliopathies: Undocking of an Extensive Ciliary Network Induces Proteostasis and Cell Fate Switching Resulting in Severe Primary Ciliary Dyskinesia

Research on Ciliary Diseases: The Role of CCDC39/CCDC40 Heterodimer in Primary Ciliary Dyskinesia Academic Background Primary Ciliary Dyskinesia (PCD) is a rare monogenic disorder characterized by chronic respiratory infections, infertility, and organ laterality defects. Although more than 50 genes associated with PCD have been identified, mutation...

Selective Abrogation of S6K2 Identifies Lipid Homeostasis as a Survival Vulnerability in MAPK Inhibitor–Resistant NRAS-Mutant Melanoma

Academic Background NRAS-mutant (NRASmut) melanoma is a highly aggressive tumor type, accounting for nearly 30% of all melanoma cases. NRAS is an oncogene that persistently activates the mitogen-activated protein kinase (MAPK) signaling pathway, which plays a critical role in melanoma development. However, despite extensive research on MAPK pathway...

Pseudomonas aeruginosa Infection Induces Lung Transplant Antibody-Mediated Rejection

Pseudomonas aeruginosa Infection Induces Antibody-Mediated Rejection in Lung Transplantation Academic Background Introduction Lung transplantation is a critical treatment for end-stage lung diseases, but post-transplant rejection remains a major challenge affecting long-term patient survival. Antibody-mediated rejection (AMR) is an increasingly rec...

Age-Dependent Macropinocytosis Drives Resistance to KRAS-G12D–Targeted Therapy in Advanced Pancreatic Cancer

Academic Background and Problem Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive cancer with an extremely low five-year survival rate, primarily due to late diagnosis and limited treatment options. Approximately 95% of PDAC patients harbor KRAS mutations, with the KRAS-G12D mutation being the most common. Although KRAS mutations have long b...

Perinatal Dysfunction of Innate Immunity in Cystic Fibrosis

Study on Congenital Immune Dysfunction in Cystic Fibrosis Research Background Cystic Fibrosis (CF) is a genetic disease caused by mutations in the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene, primarily affecting the lungs and digestive system. One of the major problems faced by CF patients is recurrent infections and inflammatio...