Senolytic CAR T Cells Reverse Senescence-Associated Pathologies

Investigators tested the therapeutic concept that chimeric antigen receptor (CAR) T cells that target senescent cells could be effective senolytic agents. They identified the urokinase-type plasminogen activator receptor (uPAR)11 as a cell-surface protein that is broadly induced during senescence and showed that uPAR-specific CAR T cells efficiently ablated senescent cells in vitro and in vivo.
[Nature]
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Eosinophil Function in Adipose Tissue Is Regulated by Krüppel-Like Factor 3 (KLF3)

Investigators examined the transcriptomic profile of adipose-resident eosinophils and posit that KLF3 regulates adipose tissue function via transcriptional control of secreted molecules linked to beiging.
[Nature Communications]
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Nanoparticle Delivery of Immunostimulatory Oligonucleotides Enhances Response to Checkpoint Inhibitor Therapeutics

Researchers found that their engineered nanoparticles carrying a CpG DNA ligand of TLR9 could suppress tumor growth in several animal models of various cancers, resulting in an abscopal effect on distant tumors, and improving responsiveness to anti-CTLA4 treatment with combinatorial effects after intratumoral administration.
[Proceedings of the National Academy of Sciences of the United States of America]
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Intratumoral Immune Activation with TLR4 Agonist Synergizes with Effector T Cells to Eradicate Established Murine Tumors

Scientists combined intratumoral administration of the synthetic toll-like receptor 4 agonist glucopyranosyl lipid A with either active vaccination or adoptive transfer of tumor-specific CD8 T cells to mice bearing established melanomas.
[Npj Vaccines]
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DNA of Neutrophil Extracellular Traps Promotes Cancer Metastasis via CCDC25

Investigators showed that neutrophil extracellular traps (NETs) were abundant in the liver metastases of patients with breast and colon cancers, and that serum NETs could predict the occurrence of liver metastases in patients with early-stage breast cancer.
[Nature]
Yang, L., Liu, Q., Zhang, X., Liu, X., Zhou, B., Chen, J., … Song, E. (2020). DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25. Nature, 1–6. https://doi.org/10.1038/s41586-020-2394-6 Cite
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A Variant in IL6ST with a Selective IL-11 Signaling Defect in Human and Mouse

Researchers characterized the impact of a variant on cytokine signaling in vitro using transfected cell lines as well as primary patient-derived cells and supported these findings using a mouse model with the corresponding genome-edited variant Il6st p.R279Q.
[Bone Research]
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convertibleCARs: A Chimeric Antigen Receptor System for Flexible Control of Activity and Antigen Targeting

An inert form of the human NKG2D extracellular domain (iNKG2D) was engineered as the ectodomain of the chimeric antigen receptor (CAR) to generate convertibleCARTM-T cells. These cells were specifically directed to kill antigen-expressing target cells only in the presence of an activating bispecific adapter comprised of an iNKG2D-exclusive ULBP2-based ligand fused to an antigen-targeting antibody
[Communications Biology]
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The Physiology, Pathology, and Potential Therapeutic Applications of the TREM2 Signaling Pathway

Investigators summarize and question what is known and remains to be discovered about the TREM2 signaling pathway, track the consequences of its activation in physiological niches and pathological contexts, and highlight the promising potential of therapeutic manipulation of TREM2 signaling.
[Cell]
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Old Dogs, New Trick: Classic Cancer Therapies Activate cGAS

The authors review the antitumor roles of the GMP-AMP synthase (cGAS-STING) pathway during tumorigenesis, cancer immune surveillance, and cancer therapies. They also highlight classic cancer therapies that elicit antitumor immune responses through cGAS activation.
[Cell Research]
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Huge Open-Access Journal Deal Inked by University of California and Springer Nature

The University of California (UC) system announced it has signed the biggest open-access deal in North America with one of the largest commercial scientific publishers. The agreement with Springer Nature includes a commitment by the publisher to explore making all articles that UC corresponding authors publish in the Nature family of journals immediately free to read on publication starting in 2022.
[ScienceInsider]
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Pro-Lymphangiogenic VEGFR-3 Signaling Modulates Memory T Cell Responses in Allergic Airway Inflammation

Researchers explored how pro-lymphangiogenic signaling affects the allergic response to house dust mite. In the acute inflammatory phase, the lungs of mice treated with blocking antibodies against VEGFR-3 displayed less inflammation overall, with dramatically reduced innate and T-cell numbers and reduced inflammatory chemokine levels.
[Mucosal Immunology]
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