bdsPredictive Immune Signatures for Chronic Graft Versus Host Disease (cGVHD) Dysregulated immune signatures may be well-suited for their ability to predict the effectiveness of agents targeting IL-17 and CSF-1. Chronic Graft Versus Host Disease (cGVHD) is the leading cause of non-relapse late morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT), affecting 30-50% of survivors. While there are an increasing number of approved therapies that target specific dysregulated immune pathways (including IL-17 and CSF1), only a minority of patients respond to any particular agent. This is consistent with a heterogeneous disease pathogenesis and the need for predictive immune signatures to choose appropriate therapy. Using single cell sequencing-based approaches, Dr. Geoffrey Hill's team at Fred Hutchinson Cancer Center has identified IL-17 and CSF-1 dysregulation signatures in informative preclinical models that are detectable in patients at and before the onset of cGVHD, allowing identification of high risk patients whilst instructing selection of appropriate therapeutic interventions. <ul> <li>Can be used to predict effectiveness of treatment response for drugs targeting IL-17 (Belumosudil) and CSF-1 (Axatilimab)</li> <li>Predictive immune signatures for the occurrence of cGVHD upto 100+ days before the onset of disease.</li> <li>Could be used for patient stratification for clinical trials focused on cGVHD and therapeutic selection</li> <li>Signatures may also be valuable in other diseases such as psoriasis, systemic sclerosis, etc.</li> </ul> <ul> <li>No immune signatures for dysregulation of these cytokine pathways currently exist.</li> </ul> <ul> <li>Geoffrey Hill, MD, FRACP, FRCPA; Director of HSCT, Sr. VP and Director of Translational Science & Therapeutics Division, Leonard and Norma Klorfine Endowed Chair for Clinical Research, Fred Hutch</li> </ul> Preclinical in vivo Provisional patent application filed FH_Hill_PredictiveImmuneSignatures_Feb2025.pdf GVHD | graft versus host disease | geoff Hill | biomarker | immune signatures | HSCT | transplantation hill-il17-csf1-signatures