Using chemokine receptors to improve cancer immunotherapy: CCR4-targeted T cell fratricide

Chimeric antigen receptor T cell (CAR-T) therapy continues to be a powerful approach for treating relapsed-refractory hematological malignancies. Despite ongoing clinical success patients remain resistant to long-term benefits of CAR-T therapy.
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Solving the Mystery of CXCL4's Role in Leukocyte Recruitment

Chemokine-matrix Interactions Promote Immune Cell Accumulation Independent of Chemokine Receptors The chemokine CXCL4 is also known as platelet factor 4 (PF4), because: it is released from  alpha-granules  of activated 
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Dendritic Cell Recruitment by the Chemokine XCL1 Improves Cancer Outcomes

XCL1 as a Potential Biomarker to Predict Durable Response to Anti-PD-1 Treatment in Non-Small Cell Lung Cancer XCL1 is secreted by activated T and NK cells. It is thought to function by promoting their engagement with antigen-presenting
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Crystal Structure of CCL21 and Identification of a Sulfotyrosine Binding Site by NMR

Custom-made 15N-enriched CCL21 protein supplied by Protein Foundry The chemokine CCL21 guides both T cell and metastatic cancer homing to lymph nodes by activating the receptor CCR7. CCL21 is among a handful of chemokines with an unstructured
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Protein Foundry’s CXCL4 Used to Identify Antibodies That Cause Heparin-Induced Thrombocytopenia

Cloned antibodies from patients with heparin-induced thrombocytopenia (HIT)  provide new clues to HIT pathogenesis A recent study published in Blood from scientists at @BloodCenterWI and @MayoClinic reveals structural differences between
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Cooperative Chemokine Signaling Influencing T Cell Movement from Blood to Tissue

Chemokine positioning assists extravasation of pathogenic human T cells
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Assays for Measuring Cell Surface Expression of CXCR4

When a chemokine binds to its G protein-coupled receptor one of the consequences of receptor activation is a decrease in the levels of receptor present on the cell surface due to more rapid internalization. The mechanism of GPCR internalization
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CXCL12 potentiates chromatin compaction via ACKR3 activation

CXCL12 and its receptor CXCR4 have well known roles in bone marrow homing and  mobilization of hematopoietic stem cells and neutrophils, but inflammatory neutrophil  recruitment is governed by CXCR2 and its
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Chemokine CXCL4 key to rare COVID-19 vaccine side effect

Chemokine CXCL4 key to rare COVID-19 vaccine side effect
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Human CXCL10 identified as a risk factor for cardiovascular disease

Plasma concentrations of inflammatory proteins can serve as biomarkers for cardiovascular disease (CVD). Previous studies had linked the T cell chemokine CXCL10/IP-10 to hypertension and heart failure, but failed to achieve the statistical significance necessary for its use as a biomarker for human disease.
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Human CXCL4 (PF4) linked to Covid-19 vaccine blood clots

As reported recently in the Wall Street Journal and other publications, the human chemokine CXCL4 (also known as platelet factor 4 or PF4) is the common link between COVID-19 vaccine-induced immune thrombotic thrombocytopenia (VITT) and a more common condition known as heparin-induced thrombocytopenia (HIT). 
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Origins of Metamorphism in XCL1

A new TiBS Spotlight features the work of Protein Foundry scientists and collaborators on the evolution of a highly unusual chemokine.
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Study reveals evolutionary origins of fold-switching protein

A shapeshifting immune system protein called XCL1 evolved from a single-shape ancestor hundreds of millions of years ago. Researchers at the Medical College of Wisconsin discovered the molecular basis for how this happened, in  a study
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Modeling ligand-receptor specificity

Using a hybrid modeling approach, Fox generated a model for the chemokine XCL1 in complex with its G protein-coupled receptor XCR1 and identified key interaction sites. Changes within a region of XCL1 that determined its binding energy to XCR1 changed the activity of the receptor and, consequently, cell migration
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