Peripheral Blood Mononuclear Cell Gene Expression Signatures Predict Long-term Survivorship in Canine DLBCL.

Area of Science:

• Immunology
• Oncology
• Veterinary Medicine

Background:

• Canine diffuse large B cell lymphoma (DLBCL) models human double-hit DLBCL.
• A clinical trial combined anti-CD20 antibody, doxorubicin, and immune modulators for DLBCL treatment in dogs.
• Previous research reported clinical outcomes and tumor biomarkers.

Purpose of the Study:

• To analyze dynamic gene expression changes in peripheral blood mononuclear cells (PBMCs) during DLBCL treatment in dogs.
• To identify immune correlates associated with early relapse versus long-term survival.
• To develop predictive biomarkers for guiding intensive treatment strategies.

Main Methods:

• Longitudinal collection of PBMCs from dogs undergoing DLBCL treatment.
• Gene expression analysis using the NanoString Canine IO panel.
• Development of quantitative PCR (qPCR) assays for key predictive genes.

Main Results:

• Elevated interferon-stimulated gene (ISG) signatures and specific immune-skewing genes (e.g., CCR9, CD209, CMKLR, DDX58) correlated with shorter survival and early relapse.
• Increased CD1E and CCL14 expression post-immunotherapy indicated association with long-term survival.
• TBHD, NPNT, and ISG20 were elevated at day 7 in dogs with shorter survival times.

Conclusions:

• PBMC gene expression analysis can predict early relapse in canine DLBCL.
• Identification of specific genes (TBHD, NPNT, ISG20) offers potential for point-of-care testing.
• Biomarker-guided treatment can inform clinical management for improved DLBCL outcomes in dogs.