Clinical Implications of Immune Checkpoints and the RANK/RANK-L Signaling Pathway in High-Grade Canine Mast Cell Tumors.

Mast cell tumors (MCTs) are the most common malignant cutaneous tumors in dogs, and they present extremely variable biological behavior. The interaction between RANK, RANK-L, and immune checkpoints is frequently detected in the tumor microenvironment, and, together, they participate in every stage of cancer development. Thus, the aim of this study was to characterize the molecular profiles of PD-L1, CTLA-4, RANK/RANK-L signaling pathway, and IFN-γ in primary tumors and lymph node metastases. Formalin-fixed, paraffin-embedded slides of MCTs and metastatic lymph nodes of ten dogs were submitted to immunohistochemical investigations. The results demonstrated that the tumor microenvironment of the high-grade mast cell tumors showed moderate or intense immunolabeling of all proteins, and the lymph node metastases also showed moderate or intense immunolabeling of checkpoint proteins. In addition, MCTs larger than 3 cm were associated with intensified PD-L1 (p = 0.03) in metastatic lymph nodes and RANK-L (p = 0.049) immunoreactivity in the tumor. Furthermore, dogs with a survival time of less than 6 months showed higher PD-L1 immunoreactivity (p = 0.042). In conclusion, high-grade MCT is associated with an immunosuppressive microenvironment that exhibits elevated RANK/RANK-L signaling and enhanced immune checkpoint immunoreactivity, potentially facilitating intratumorally immune escape. These biomarkers show promise as clinical indicators of disease progression and might response to immunotherapy in dogs with high-grade MCTs, thus emphasizing their importance for guiding treatment decisions and improving outcomes.

Use of an allogenous tunica vaginalis conserved in 98% glycerine for keratoplasty in dogs

We evaluated the use of an allogenous tunica vaginalis conserved in 98% glycerine for lamellar keratoplasty in dogs. Sevendogs were submitted to keratoplasty and clinically evaluated during the initial (1 to 15 days), intermediate (16 to 30 days) and late(31 to 120 days) postoperative periods. The corneas were evaluated by light microscopy at 1, 3, 7, 15, 30, 60 and 120 days aftersurgery. Photophobia, epiphora, blepharospasm, corneal edema, ocular secretion and chemosis were observed during theinitial periods, and tended to disappear during the intermediate periods. Vascular neoformation started around the 4th day, witha maximum intensity on the 25th day and a gradual regression thereafter, and tended to disappear between the 60th and 120thday. The graft itself and adjacent areas showed a tendency towards the reestablishment of transparency during the latepostoperative periods. With respect to morphology, an inflammatory infiltrate characterized by the invasion of polymorphonuclearand mononuclear leukocytes was observed which disappeared by the 60th postoperative day, when the graft was found to beincorporated and the stroma returned to normal. The present results led us to conclude that the allogenous tunica vaginalisconserved in 98% glycerine was feasible and efficient for lamellar keratoplasty in dogs.