@Geoff_Hill_Lab

Hill Lab (run by lab members) @FredHutch #BMT #GVHD #immunotherapy #myeloma

 Fred Hutchinson
research.fhcrc.org/geoff-hill/en/research-overview.html
Joined February 2020
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New paper out today showing that IL6R inhibition during cellular immunotherapy promotes expansion of cytolytic CD4 T cells. Awesome collab between QIMR, Uni of Melb, and Fred Hutch. Check it out and the accompanying commentary in Blood! ashpublications.org/blood/ar…

IL-6 receptor inhibition promotes expansion of cytolytic CD4+ T cells after cellular immunotherapy

Key PointsIL-6R inhibition during HSCT promotes type I interferon signaling in blood monocytes and CD4+ T cells.IL-6R inhibition during cellular immunother

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New paper hot off the press! Here, we demonstrate that IL-6R inhibition during either bone marrow transplantation or CAR T cell therapy promotes the expansion of cytolytic CD4+ T cells, which are associated with favorable immunotherapy outcomes. ashpublications.org/blood/ar…

IL-6 receptor inhibition promotes expansion of cytolytic CD4+ T cells after cellular immunotherapy

Key PointsIL-6R inhibition during HSCT promotes type I interferon signaling in blood monocytes and CD4+ T cells.IL-6R inhibition during cellular immunother

ashpublications.org
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New paper alert! Led by@simone_minnie, we describe a promising and clinically testable combination of anti-CSF1R therapy and lenalidomide to improve outcomes after autologous stem cell transplant for myeloma. Check it out now! ashpublications.org/blood/ar…

CSF-1R inhibition and lenalidomide synergize to promote myeloma control after autologous stem cell...

Key PointsCSF-1R+CD163+CD169+ macrophages are expanded in the bone marrow of patients with relapsed myeloma after ASCT.Combining CSF-1R blockade with lenal

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Our colleagues from Monash University and Lions Eye Institute in Australia discovered a novel stroma-based mechanism that is critical for generating effective antiviral T cell responses against cytomegalovirus. Read it now in Nature! nature.com/articles/s41586-0…

Fibroblastic reticular cells direct the initiation of T cell responses via CD44

Nature - CD44 expressed by fibroblastic reticular cells in secondary lymphoid organs regulates trafficking of dendritic cells, and thus has an essential role in the priming of T cells and the...

nature.com
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PTCy prevents both severe acute and chronic GVHD. In our new review published in Blood, Dr Geoffrey Hill and Dr David Curtis discuss the current landscape of GVHD prophylaxis, key unanswered questions, and what’s next in the BMT field in the PTCy era. ashpublications.org/blood/ar…

Posttransplant cyclophosphamide in HLA-matched peripheral blood transplantation: what’s next?

Prevention of acute and chronic graft-versus-host disease (GVHD) remains a priority area for improvement in allogeneic hematopoietic stem cell transplantat

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New paper out now! Led by Dr Motoko Koyama, we’ve clarified the role of various donor dendritic cell subsets in gastrointestinal acute GVHD and discuss strategies to target these populations to prevent lethal gut GVHD early after BMT. ashpublications.org/blood/ar…

Targeting donor XCR1+ and CD11b+ dendritic cells prevents Th1- and Th17-dependent GVHD within the...

Key PointsDonor XCR1+ cDC present high amounts of alloantigen to induce Th1 differentiation and imprint gut homing integrin expression during gut GVHD.Dono

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New publication alert! Eomes drives differentiation of type-1 regulatory CD4 T cells that are critical for limiting immune toxicity and tumor relapse after T cell immunotherapy through dual regulatory and cytotoxic functions. Check it out! @ImmunityCP cell.com/immunity/fulltext/S…
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Eomes controls the acquisition of regulatory and cytotoxic function in CD4+ T cells that are critical for limiting immune toxicity, while maintaining persistence and tumor control after immunotherapy @ImmunityCP cell.com/immunity/fulltext/S… @fredhutch @Geoff_Hill_Lab 🇺🇸
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Graft-versus-Host Disease Prophylaxis with Cyclophosphamide and Cyclosporin | New England Journal of Medicine nejm.org/doi/full/10.1056/NE…

Graft-versus-Host Disease Prophylaxis with Cyclophosphamide and Cyclosporin | NEJM

Allogeneic peripheral-blood stem-cell transplantation (SCT) from a matched related donor after myeloablative conditioning is the preferred curative treatment for patients with high-risk blood cance...

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Graft-versus-Host Disease Prophylaxis with Cyclophosphamide and Cyclosporin | New England Journal of Medicine nejm.org/doi/full/10.1056/NE…

Graft-versus-Host Disease Prophylaxis with Cyclophosphamide and Cyclosporin | NEJM

Allogeneic peripheral-blood stem-cell transplantation (SCT) from a matched related donor after myeloablative conditioning is the preferred curative treatment for patients with high-risk blood cance...

nejm.org
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New work out of the lab! @julieboiko has identified tractable monocyte gene signatures of IL-17 and CSF1-driven chronic GVHD that can be extended to patients. ashpublications.org/blood/ar… First edition preview out now!

Defining pathogenic IL-17 and CSF-1 gene expression signatures in chronic graft-versus-host disease

Key PointsTemporal single-cell RNA sequencing of mouse blood identifies nonintuitive signatures of IL-17 and CSF-1 dysregulation during cGVHD.Analogous IL-

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We have written a reply to a letter to the Editor about our recent paper looking at the effects of calcineurin inhibitors on T cell differentiation after alloBMT. doi.org/10.1172/JCI184869
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This open exchange between two research groups is a great example of how we can discuss papers that report what appear to be contradictory results. Long story short, the biology is actually largely the same, but the terminology and assignment of T cell subsets is different.
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I’m excited to share what has been 5 years in the making (my first project in the lab starting as a heme/onc fellow)! Microbiota dictate T cell clonal selection to augment graft-vs-host-disease following stem cell transplant. @ImmunityCP @Geoff_Hill_Lab cell.com/immunity/fulltext/S…
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New paper out of the lab! We found that calcineurin inhibitors prevented differentiation of exhausted T cells after allogeneic BMT. Rather, these T cells became memory cells and were able to cause chronic GVHD after drug removal. doi.org/10.1172/JCI170125
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Treg depletion during SCM expands polyfunctional effector T cells in mobilized grafts and enhances antimyeloma immunity after ASCT. ow.ly/syjV50RjakL #transplantation #immunobiologyandimmunotherapy
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For open access to our recent manuscript describing T cells that retained functional capacity despite a terminally exhausted phenotype, visit the Hill Lab webpage via the link below and scroll down to the myeloma section! research.fredhutch.org/geoff…

Research Overview

Research overview of Dr. Geoffrey Hill's lab at Fred Hutch Cancer Center.

research.fredhutch.org
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My fave postdoc project is out today!! This manuscript has been a labor of love and I'm so excited to finally share it with the broader immunology community. science.org/doi/10.1126/scii…

TIM-3+ CD8 T cells with a terminally exhausted phenotype retain functional capacity in hematologi...

A subset of CD8 T cells with a terminally exhausted epigenetic profile expressed IFN-γ, granzymes, and perforin in bone marrow.

science.org
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Next paper out of the @Geoff_Hill_Lab!! Regulatory T cells suppress myeloma-specific immunity during autologous stem cell mobilization and transplantation ashpublications.org/blood/ar…

Regulatory T cells suppress myeloma-specific immunity during autologous stem cell mobilization and...

T cells from bone marrow egress to blood during SCM and preferentially home back to marrow after adoptive transfer.Treg depletion during SCM expands polyfu

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