Lymph-node transcriptomics define prognostic immune states in mucosal melanoma and reveal IBA1 as a practical biomarker for improved prognosis
Mucosal melanoma (MM) is a rare and aggressive cancer in humans with poor prognosis and limited response to immunotherapy or targeted therapy. Progress has been hindered by the lack of immune-competent, translational models. Dogs develop oral mucosal melanoma (OMM), a biologically equivalent disease, making them a valuable companion animal model that shares the human environment and immune context. In this study, we present the first transcriptomic analysis of regional lymph nodes in dogs with OMM, revealing that lymph nodes stratify into two distinct subgroups, independent of histopathological metastatic status at time of surgery, and which can be succinctly captured with a 35-gene signature. Notably, this stratification correlates with survival outcomes, providing unique early prognostic insights at the time of diagnosis. Furthermore, we explore the immune landscape of these subgroups and identify IBA1+ monocyte/macrophage infiltration as a key distinguishing biomarker. Using immunohistochemistry (IHC) and digital pathology, we demonstrate that higher IBA1 expression is associated with the transcriptomic subgroups associated with improved survival. These findings highlight IBA1 as a potential biomarker for risk stratification, offering a clinically relevant tool for refining prognosis and guiding treatment decisions in canine OMM. HighlightsO_LITranscriptomic profiling of canine OMM lymph nodes identifies two prognostic subgroups, independent of histopathological metastatic status. C_LIO_LILymph node transcriptomic stratification correlates with survival, providing prognostic insights beyond conventional histopathology at the time of diagnosis. C_LIO_LIIBA1+ monocyte/macrophage infiltration is associated with improved survival, and shows strong diagnostic potential via immunohistochemistry, supporting its use as a clinically feasible stratification tool. C_LI