PD-L2 reverse signaling suppresses tumor cell proliferation and serves as a prognostic indicator in canine high-grade mast cell tumors.

PD-L2 expression predicts better prognosis in canine high-grade mast cell tumors.

This study investigated PD-L2 expression in canine mast cell tumors (MCTs) as a potential prognostic biomarker and immune regulator. Researchers analyzed 38 canine MCTs (15 low-grade, 23 high-grade) using immunohistochemistry, finding that low-grade tumors expressed high levels of PD-L2 (median 83.5%), while high-grade tumors showed variable expression (median 25.5%). Surprisingly, high-grade MCT cases with lower PD-L2 expression demonstrated significantly worse prognosis (148 days median survival) compared to those with higher expression (468 days). This counterintuitive finding prompted investigation of PD-L2 reverse signaling mechanisms. In vitro studies using adenovirus-mediated PD-L2 gene transfer in canine MCT cells revealed that PD-1-PD-L2 interaction suppressed tumor cell proliferation and altered expression of 70 genes. The findings suggest that PD-L2 functions as a tumor-suppressive mechanism through reverse signaling rather than immune evasion. These results establish PD-L2 as a significant prognostic indicator in canine high-grade MCTs and reveal a novel regulatory pathway in canine tumor biology with potential therapeutic implications.

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