Results 171 to 180 of about 211,137 (291)

T‐Cell Exhaustion in the Tumor Microenvironment: Subcellular Dysfunction, Pan‐Cancer Characteristics, and Therapeutic Interventions

open access: yesAdvanced Science, EarlyView.
This study elucidates the mechanisms of subcellular multidimensional collapse in exhausted T cells. By specifically targeting the nucleus, mitochondria, and endoplasmic reticulum, strategic interventions can effectively remodel the compromised organelle network. This integrated approach drives comprehensive T cell resuscitation, ultimately establishing
Mingxing Wang   +9 more
wiley   +1 more source

A Plug‐and‐Play Platform for Customizing Multivalent Degraders and Degrader‐Drug Conjugates

open access: yesAdvanced Science, EarlyView.
Membrane proteins remain challenging targets for conventional TPD approaches. Here, the authors develop UPTAB, a modular platform leveraging ultrahigh‐affinity orthogonal Im/CL protein pairs for lysosomal degradation of membrane proteins. Mono‐targeted (Type‐I), dual‐targeted (Type‐II), and tri‐targeted (Type‐III) UPTABs enable simultaneous degradation
Mengqing Zhao   +7 more
wiley   +1 more source

Targeting PLD3 Reverses the Immunosuppressive Niche by Reprogramming Tumor‐Associated Macrophages and Potentiates Antitumor Immunity

open access: yesAdvanced Science, EarlyView.
PLD3 activates the lysosomal‐AKT‐NF‐κB axis to drive cellular senescence in macrophages, establishing an immunosuppressive TME by limiting the infiltration of cytotoxic T, NK, and NKT cells, which confers resistance to anti‐PD‐1 therapy. Abrine inhibits PLD3 expression, restoring antitumor immunity and synergizing with anti‐PD‐1 treatment.
Xingtu Qin   +11 more
wiley   +1 more source

ABHD17C‐Mediated S‐Depalmitoylation of BCL6B Enhances CD24 Transcription to Resist Macrophage Phagocytosis in Pancreatic Cancer

open access: yesAdvanced Science, EarlyView.
ABHD17C‐mediated depalmitoylation of BCL6B at Cys442 blocks its nuclear import and triggers ubiquitin‐dependent degradation, attenuating transcriptional repression of the anti‐phagocytic signal CD24. This mechanism enables pancreatic cancer cells to evade macrophage phagocytosis and fosters an immunosuppressive microenvironment.
Yalu Zhang   +9 more
wiley   +1 more source

Aptamer‐Targeted PrPC Drives Colorectal Cancer Metastasis via a LYN‐STAT3 Complex and Enables Liquid Biopsy Detection

open access: yesAdvanced Science, EarlyView.
The aptamer WHY‐3E identifies PrPC as a CRC driver. Stabilized by USP18, endocytosed PrPC forms a LYN/STAT3 complex, upregulating MSN transcription to promote metastasis. Crucially, WHY‐3E sensitively detects PrPC‐positive circulating exosomes, establishing a robust theoretical foundation for non‐invasive clinical diagnostics.
Chunlin Wang   +23 more
wiley   +1 more source

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