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Articles by Victor Tkachev
Algorithmically Reconstructed Molecular Pathways as the New Generation of Prognostic Molecular Biomarkers in Human Solid Cancers
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Notch signaling drives intestinal graft-versus-host disease in mice and nonhuman primates
Abstract Notch signaling promotes T cell pathogenicity and graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT) in mice, with a dominant role for the Delta-like Notch ligand DLL4. To assess whether Notch’s effects are evolutionarily conserved and to identify the mechanisms of Notch signaling inhibition, we studied antibody-mediated DLL4 blockade in a nonhuman primate (NHP) model similar to human allo-HCT.
Notch signaling drives intestinal graft-versus-host disease in mice and nonhuman primates
Abstract Notch signaling promotes T cell pathogenicity and graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT) in mice, with a dominant role for the Delta-like Notch ligand DLL4. To assess whether Notch’s effects are evolutionarily conserved and to identify the mechanisms of Notch signaling inhibition, we studied antibody-mediated DLL4 blockade in a nonhuman primate (NHP) model similar to human allo-HCT.
Spatiotemporal single-cell profiling reveals that invasive and tissue-resident memory donor CD8+ T cells drive gastrointestinal acute graft-versus-host disease
SIVSing through GVHD Currently, there are few ways to track leukocyte movements in vivo. Potter and colleagues developed a method to track leukocyte migration in vivo called serial intravascular staining or SIVS. The authors infused differently labeled antibodies at different time points to reveal distinct leukocyte population kinetics in healthy macaques and those infected with Mycobacterium tuberculosis. Tkachev et al.
Measurement of leukocyte trafficking kinetics in macaques by serial intravascular staining
SIVSing through GVHD Currently, there are few ways to track leukocyte movements in vivo. Potter and colleagues developed a method to track leukocyte migration in vivo called serial intravascular staining or SIVS. The authors infused differently labeled antibodies at different time points to reveal distinct leukocyte population kinetics in healthy macaques and those infected with Mycobacterium tuberculosis. Tkachev et al.
Spatiotemporal single-cell profiling reveals that invasive and tissue-resident memory donor CD8+ T cells drive gastrointestinal acute graft-versus-host disease
Victor Tkachev https://orcid.org/0000-0001-6011-0576 , James Kaminski https://orcid.org/0000-0002-5137-7516, E. Lake Potter https://orcid.org/0000-0003-4339-9800, Scott N. Furlan, Alison Yu, Daniel J.
Author Correction: Innovations present in the primate interneuron repertoire
Correction to: Nature https://doi.org/10.1038/s41586-020-2781-z Published online 30 September 2020 In Figure 2b of this Article, two labels were inadvertently swapped: the brown dot should be labelled ‘PVALB+’, and the yellow dot should be labelled ‘SST+’. In addition, the y-axis label of Fig. 4g should read “Percentage of striatal interneurons” not “Striatal interneurons (%)” and the numbers on the axis should be 0, 10, 20, 30, 40 (rather than 0, 0.1, 0.2, 0.3, 0.4).
Innovations present in the primate interneuron repertoire
Abstract Primates and rodents, which descended from a common ancestor around 90 million years ago1, exhibit profound differences in behaviour and cognitive capacity; the cellular basis for these differences is unknown. Here we use single-nucleus RNA sequencing to profile RNA expression in 188,776 individual interneurons across homologous brain regions from three primates (human, macaque and marmoset), a rodent (mouse) and a weasel (ferret).
CD28 blockade controls T cell activation to prevent graft-versus-host disease in primates
CD28 blockade: pharmacokinetics, pharmacodynamics, and donor engraftment. In this study, CD28 blockade with FR104 was evaluated either as monoprophylaxis or in combination with sirolimus for its ability to prevent GVHD in the setting of MHC-haploidentical T cell–replete HCT (Figure 1A). Figure 1B shows the resulting FR104 pharmacokinetics (PKs) in the current study.
Combined OX40L and mTOR blockade controls effector T cell activation while preserving Treg reconstitution after transplant
Graft-versus-host disease (GVHD) after stem cell transplantation is mediated by effector T cells derived from donor stem cells, but GVHD can also be abrogated by donor-derived regulatory T cells. GVHD prophylaxis ideally should then allow regulatory T cell responses while inhibiting effector T cells. Tkachev et al. now provide very promising results in a nonhuman primate model, which suggest that such therapy is possible.
Biological role of T Memory Stem Cells as a Cellular Reservoir for Graft-versus-Host Disease
T memory stem cells (Tscm) are a subset of antigen-experienced, long-lived, self-renewing and multipotent T cells, which reconstitute immunity following hematopoietic cell transplantation (HCT). Here we investigated the biological role of Tscm in acute Graft-versus-Host Disease (GVHD) using a translational non-human primate model.
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