👏 I would like to thank all our collaborators, especially @sophielg2131.bsky.social for her outstanding work and Nicolas Vallet, all our funder Fédération Leucémie Espoir, Fondation Maladies Rares-HPN France Aplasie Medullaire, Fonds de dotation CSL behring, Siric InSitu and InIdEx immuno-oncology

This work is the result of a truly collaborative effort between @inserm.fr @institut-leucemie.bsky.social @ap-hp.bsky.social @upcite.bsky.social @cryostem @siric InSitu and @InIdEx Immuno-Oncology

🚀 These results have major implications for patients and suggest that:
•steroid resistance could be predicted early,
•treatment strategies might need to be adapted upfront,
•and that inflammasome and IL-1 could represent promising therapeutic targets in GvHD.

•activation of the inflammasome and caspase-1,
•a pro-inflammatory environment involving TNFα, IL-1β and IL-18 signaling,
•specific interaction network between myeloid and T cells involving IL-18, CCL3 and CCL4 
•and a distinct trajectory of CD8+ T cells

🔬 Our data reveal that the biological programs associated with steroid resistance are already present at disease onset.
Rather than being a secondary phenomenon, resistance appears to be driven by an early immune program characterized by:

👉 why do some patients fail to respond to steroids whereas other patients develop steroid-sensitive GVHD?
 
We addressed this question by analyzing patient samples from two cohorts of patients from @Cryostem biobank, collected at the very onset of GVHD, before corticosteroids

👉 Acute graft-versus-host disease (GVHD) remains one of the major complications after #alloHSCT. While corticosteroids are still the cornerstone of first-line treatment, nearly half of patients will not respond to treatment and will require additional immunosuppressive drugs.

Corticosteroid resistance is predetermined by early immune response dynamics at acute graft-versus-host disease onset Steroid-resistant acute graft-versus-host disease is set at disease onset and leads to distinct cell-to-cell cross-talk and immune trajectories.

New in @science.org
🧬 Thrilled to share our last paper

Corticosteroid resistance is predetermined by early immune response dynamics at acute graft-versus-host disease onset | Science Translational Medicine #ScienceTranslationalMedicineResearch www.science.org/doi/10.1126/...

A spatial atlas of human gastrointestinal acute GVHD reveals epithelial and immune dynamics underlying disease pathophysiology Multiplexed imaging of aGVHD GI biopsies revealed epithelial remodeling and alteration in immune composition, offering insight into disease pathology.

Happy to share our article in collaboration with @leeat-keren.bsky.social at Weizmann Institute of Science and @institut-leucemie.bsky.social A spatial atlas of human gastrointestinal acute GVHD reveals epithelial and immune dynamics underlying disease pathophysiology www.science.org/doi/10.1126/...

doi.org/10.1084/jem....

Great collaboration with the group of Robert Zeiser linking microbiota-derived metabolites and central nervous system GVHD

Diet outperforms microbial transplant to drive microbiome recovery in mice - Nature Experiments in mouse models show that proper recovery of the intestinal microbiota following depletion, with or without faecal microbiota transplant therapy, is dependent on syntrophic interactions th...

www.nature.com/articles/s41...

Teduglutide for treatment-refractory severe intestinal acute graft-versus-host disease - a multicenter survey Bone Marrow Transplantation - Teduglutide for treatment-refractory severe intestinal acute graft-versus-host disease - a multicenter survey

Great collaboration with Robert Zeiser @institut-leucemie.bsky.social @upcite.bsky.social @ap-hp.bsky.social @insermpresse.bsky.social Teduglutide for treatment-refractory severe intestinal acute graft-versus-host disease - a multicenter survey @springernature.com @BMT journal

rdcu.be/ehWV5

Efficacy and safety of belumosudil for treatment of cGVHD: multicenter retrospective analysis of the French cohort of the compassionate use program, on behalf of the French Society of Bone Marrow Transplantation and Cellular Therapy Bone Marrow Transplantation - Efficacy and safety of belumosudil for treatment of cGVHD: multicenter retrospective analysis of the French cohort of the compassionate use program, on behalf of the...

Happy to share our last paper, published with @springernature.com in @BMTjournal, about the French experience with belumosudil in the treatment of steroid-resistant cGvHD. Best ORR 57.4% including 14.7% of CR in patients who previously received at least 2 LOT
rdcu.be/efZg9

HLA evolutionary divergence score after donor lymphocyte infusion following allogeneic hematopoietic stem cell transplantation Donor lymphocyte infusion (DLI) prevents acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) relapses following hematopoietic stem cell transplantation. Given the life-threatening toxiciti....

Congratulations to Sophie Le Grand for her very interesting paper in Hemasphere about the role of HLA evolutionary divergence score to predict outcome of prophylactic donor lymphocyte infusion after alloHSCT

doi.org/10.1002/hem3...

Systems-level immunomonitoring in children with solid tumors to enable precision medicine In a population-based cohort of 191 children with diverse solid tumors, systems-level analyses unravel immune variation with age and tumor type and provide a reference for future precision immunothera...

Systems-level immunomonitoring in children with solid tumors to enable precision medicine: Cell www.cell.com/cell/fulltex...