Inhibitory checkpoint molecule mRNA expression in canine soft tissue sarcoma

Area of Science:

• Veterinary Oncology
• Immunology
• Cancer Biology

Background:

• Canine soft tissue sarcomas (STS) are common and characterized by an immunosuppressive tumor microenvironment.
• Tumor-infiltrating lymphocytes are sparse in STS, often localized peripherally or around blood vessels.
• Overexpression of programmed cell death-axis (PD-axis) molecules is linked to immunosuppression and poor prognosis in various cancers.

Purpose of the Study:

• To investigate the expression of PD-1, PD-L1, and PD-L2 in canine STS across different tumor grades.
• To evaluate the impact of tumor ablation treatment (histotripsy) on the expression of these immune checkpoint molecules.
• To understand the relationship between PD-axis expression, tumor grade, and potential immune cell infiltration in canine STS.

Main Methods:

• Gene expression analysis using reverse-transcriptase real-time quantitative PCR (RT-qPCR).
• Analysis of untreated canine STS tissue samples representing grades 1, 2, and 3.
• Comparison of PD-1, PD-L1, and PD-L2 expression in tumor tissue before and after histotripsy treatment.

Main Results:

• PD-1, PD-L1, and PD-L2 expression was detected in all grades of untreated canine STS.
• A numerical decrease in the expression of all three markers was observed at the histotripsy treatment interface compared to untreated tumor areas.
• Higher tumor grades showed relatively increased expression of these checkpoint molecules, consistent with malignancy.

Conclusions:

• PD-axis molecules are expressed in canine STS and their expression correlates with tumor grade.
• Histotripsy treatment may reduce the expression of PD-1, PD-L1, and PD-L2 at the treatment interface.
• Reduced expression of these markers post-treatment could potentially facilitate tumor-infiltrating lymphocyte infiltration, offering a therapeutic avenue.