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

Area of Science:

• Immunology
• Hematopoietic Cell Transplantation
• Molecular Biology

Background:

• Chronic graft-versus-host disease (cGVHD) is a major complication after allogeneic hematopoietic cell transplantation (HCT), leading to significant morbidity and mortality.
• Current therapies targeting cytokines like interleukin-17 (IL-17) and colony-stimulating factor 1 (CSF-1) show efficacy in only a subset of patients and are often used empirically.
• There is a critical need for biomarkers to identify patients who will respond to specific treatments or require preemptive therapy.

Purpose of the Study:

• To develop a method for identifying specific immune signatures related to IL-17 and CSF-1 in preclinical models of cGVHD.
• To validate these signatures in patient samples to predict response to targeted therapies.
• To facilitate personalized treatment selection for cGVHD.

Main Methods:

• Utilized single-cell sequencing approaches in preclinical mouse models of cGVHD.
• Defined temporal IL-17 and CSF-1 signatures in mouse blood monocytes.
• Interrogated these signatures in monocyte populations from patients diagnosed with cGVHD and those at risk post-HCT.

Main Results:

• Identified distinct, nonintuitive IL-17 and CSF-1 signatures in mouse blood monocytes.
• Detected these signatures in relevant monocyte populations in 70% of cGVHD patients at diagnosis.
• Found signatures in 50% of patients at day +100 post-HCT who later developed cGVHD.

Conclusions:

• Monocyte-based IL-17 and CSF-1 signatures can be identified in a significant proportion of cGVHD patients.
• These signatures hold promise for prospectively identifying potential responders and nonresponders to targeted therapies.
• This approach could lead to more personalized and effective treatment strategies for cGVHD.