Results 151 to 160 of about 51,112 (243)

T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities

open access: yesAdvanced Science, EarlyView.
T cell exhaustion limits immunotherapy efficacy. This article delineates its progression from stem‐like to terminally exhausted states, governed by persistent antigen, transcription factors, epigenetics, and metabolism. It maps the exhaustion landscape in the TME and proposes integrated reversal strategies, providing a translational roadmap to overcome
Yang Yu   +7 more
wiley   +1 more source

An Implantable Scaffold Sequentially Releasing STING Agonist and B7‐H3 Antibody for Bone Metastasis Immunotherapy

open access: yesAdvanced Science, EarlyView.
We developed an implantable dual‐drug depot using GelMA for bone metastasis treatment, co‐delivering MSA‐2 and αB7‐H3‐loaded CaCO3 microparticles. Sustained release from GelMA scaffold enables MSA‐2 to activate STING signaling and enhance T‐cell infiltration and activation, while sequentially released αB7‐H3 blocks MSA‐2‐induced B7‐H3 upregulation ...
Qijun Lin   +10 more
wiley   +1 more source

Targeting WTAP/ROR1/WNT5A‐Mediated Crosstalk Between Glioma Stem Cells and Macrophages to Normalize Tumor Vasculature and Enhance Chemotherapy

open access: yesAdvanced Science, EarlyView.
In hypoxic microenvironment, WNT5A is predominantly secreted by tumor‐associated macrophages. Hypoxia‐induced WTAP mediates ROR1 stability by m6A modifications in a HuR‐dependent manner in Glioma stem cells (GSCs). WNT5A activates the WNT pathway via ROR1 binding on GSCs, driving glioma‐derived endothelial cells (GDECs) differentiation.
Xiaoyong Chen   +15 more
wiley   +1 more source

Synergistic Activation of Immunogenic Cell Death and the cGAS–STING Pathway by Engineered Zinc/Manganese‐Based Metal–Organic Framework Nanoplatforms for Colon Cancer Immunotherapy

open access: yesAdvanced Science, EarlyView.
A zinc/manganese (Zn/Mn)‐based metal‐organic framework (MOF) loaded with the STING agonist c‐di‐AMP diammonium (denoted AMP@Zn/Mn‐MOF) was developed to synergistically activate the cGAS‐STING pathway and induce immunogenic cell death. This nanoplatform reprograms the immunosuppressive tumor microenvironment, significantly enhancing anti‐PD‐L1 ...
Bingzi Zhu   +15 more
wiley   +1 more source

Pancancer Fine‐Mapping of Mutational Intolerance Identifies CHEK1 as an Immunosuppressive Driver in Lung Adenocarcinoma

open access: yesAdvanced Science, EarlyView.
This study identifies mutation‐intolerant genes (MIGs), which are mutationally constrained in tumors despite normal‐tissue variability. Using miDriver, the authors pinpoint MIGs essential for tumor‐intrinsic fitness and immune evasion. Focusing on CHEK1, they show it drives tumor fitness and sculpts an immunosuppressive niche via the MIF–CD74 axis ...
Tao Wang   +16 more
wiley   +1 more source

Mapping CSC‐Mediated Ovarian Cancer Chemoresistance via CXCR4‐PET to Guide Precision Cisplatin Re‐Sensitization Therapy

open access: yesAdvanced Science, EarlyView.
CXCR4 functions as a potential cancer stem cell‐associated marker linked to chemoresistance in ovarian cancer, and an inhibitor of CXCR4, AMD3100, can enhance the cytotoxic response to cisplatin. Based on these findings, [68Ga]Ga‐Pentixafor positron emission tomography enables selective visualization of CXCR4‐high ovarian cancer, while AMD3100 combined
Lixia Feng   +12 more
wiley   +1 more source

Phosphatidic Acid‐TRIM59‐Olig2 Signaling Couples Metabolic Dysfunction to Myelination Failure in PWMI

open access: yesAdvanced Science, EarlyView.
PA accumulates after hypoxic‐ischemic injury and stabilizes the E3 ligase TRIM59 in OPCs. Stabilized TRIM59 enhances ubiquitination and degradation of Olig2, blocking differentiation and causing hypomyelination in PWMI. Modulating PA synthesis restores Olig2 levels, improves myelination, and ameliorates behavioral deficits, defining a metabolically ...
Xinyu Li   +8 more
wiley   +1 more source

Generation of CCR4/CD7 Bispecific CAR‐T Cells Resistant to Fratricide and Exhaustion

open access: yesAdvanced Science, EarlyView.
The applications of CAR T‐cell therapy in T‐cell malignancies face limitations such as fratricide, effector‐cell exhaustion, and antigen‐escape. Herein, we developed fratricide‐ and exhaustion‐resistant CAR‐T cells that targeted CCR4 and CD7 simultaneously, with optional EGFRt safety switch. Additionally, scRNA‐seq unveiled new molecular targets, which
Sile Li   +10 more
wiley   +1 more source

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