Results 161 to 170 of about 372,429 (303)

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

Profiling Localized Immunomodulation and Drug Biodistribution within a Subcutaneous Vascularized Niche for Cell Transplantation

open access: yesAdvanced Science, EarlyView.
We studied how five common immunosuppressants behave when delivered directly to a transplant site instead of systemically. Using a vascularized implant for islet transplantation, we show that local delivery protects grafts, limits drug spread to the rest of the body, and produces distinct immune signatures.
Jocelyn Nikita Campa‐Carranza   +19 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

Studying Macromolecular Composition in Cell–Cell Interfaces Using 3D Membrane Reconstitution Systems

open access: yesAdvanced Science, EarlyView.
A comprehensive understanding of the interactions between proteins, lipids and glycocalyx components at the immune synapse is still lacking. Here, an artificial and a semi‐artificial model contact system were established to reconstitute the cell‐cell contact in 3D. The model systems enable the examination of macromolecule enrichment or depletion at the
Franziska Ragaller   +9 more
wiley   +1 more source

Dynamic Shifts in ER–Plasma Membrane Junctions Signaling Define Pro‐Metastatic N‐Glycosylation and Predict Prostate Cancer Progression

open access: yesAdvanced Science, EarlyView.
Prostate cancer remains a leading cause of male cancer death, yet screening cannot reliably identify aggressive disease, underscoring the need for tissue biomarkers. It is shown that primary tumors increase ER–plasma membrane junction signaling via STIM1/ORP5, whereas metastasis features their loss, Golgi dispersal, and rapid conversion of high‐mannose
Amanda J. Macke   +14 more
wiley   +1 more source

S100A14 in Tumor‐Derived EVs Targets PIAS3 to Reprogram Astrocytes and Induce Immunosuppressive Microenvironment Promoting Brain Metastasis and Germacrone Reversal Effect

open access: yesAdvanced Science, EarlyView.
This study identifies S100A14 in tumor‐derived exosomes as a key driver of brain metastasis. S100A14 targets PIAS3 in astrocytes, activating STAT3 signaling and promoting immunosuppressive MDSCs recruitment via chemokine secretion. Germacrone, a natural compound, binds S100A14 to disrupt this axis, effectively inhibiting brain metastasis with low ...
Qian Feng   +13 more
wiley   +1 more source

Deciphering the Evolution Pattern of Structural Variations Overlapped With Repetitive Sequence During Cattle Evolution

open access: yesAdvanced Science, EarlyView.
The authors complement bovine pan‐SV with massive novel structural variations (SVs) identified through long‐read sequencing of 83 globally distributed cattle breeds. Repetitive sequence‐mediated SVs (rep‐SV) exhibit distinct dynamic patterns throughout cattle sub‐speciation and/or domestication processes, including uneven distribution between chr‐X and
Zhifan Guo   +16 more
wiley   +1 more source

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