Canine Melanoma Immunology and Immunotherapy: Relevance of Translational Research

Abstract

In veterinary oncology, canine melanoma is still a fatal disease for which innovative and long-lasting curative treatments are urgently required. Considering the similarities between canine and human melanoma and the clinical revolution that immunotherapy has instigated in the treatment of human melanoma patients, special attention must be paid to advancements in tumor immunology research in the veterinary field. Herein, we aim to discuss the most relevant knowledge on the immune landscape of canine melanoma and the most promising immunotherapeutic approaches under investigation. Particular attention will be dedicated to anti-cancer vaccination, and, especially, to the encouraging clinical results that we have obtained with DNA vaccines directed against chondroitin sulfate proteoglycan 4 (CSPG4), which is an appealing tumor-associated antigen with a key oncogenic role in both canine and human melanoma. In parallel with advances in therapeutic options, progress in the identification of easily accessible biomarkers to improve the diagnosis and the prognosis of melanoma should be sought, with circulating small extracellular vesicles emerging as strategically relevant players. Translational advances in melanoma management, whether achieved in the human or veterinary fields, may drive improvements with mutual clinical benefits for both human and canine patients; this is where the strength of comparative oncology lies.

Cyclooxygenase-2 (COX-2) Expression in Equine Melanocytic Tumors

“…Immunotherapy is one of the major research areas in oncology [ 70 , 71 ]. PD-1/PD-L1 blockade is one of the most recently developed types of immunotherapy, and despite good results, this therapy is already facing some resistance [ 72 , 73 , 74 ].…”

Programmed Cell Death-Ligand 1 (PD-L1) Immunohistochemical Expression in Equine Melanocytic Tumors

“…Tumors have numerous mechanisms to suppress anti-tumor immune responses, allowing immune evasion and disease progression. One of these mechanisms is the up-regulation of coinhibitory receptors, also known as immune checkpoints [ 40 , 41 , 42 ].…”

“…Regarding canine melanoma, studies on this therapy are scarce; however, there is already some evidence that supports PD-1/PD-L1 blockade as a potential therapy for this type of tumor. No severe adverse effects were reported after treatment, and tumor mass regression and longer survival time were observed even in dogs which had pulmonary metastasis [ 40 , 48 , 49 , 50 , 51 , 52 ].…”

Protein phosphatase 6 regulates trametinib sensitivity, a mitogen-activated protein kinase kinase (MEK) inhibitor, by regulating MEK1/2-ERK1/2 signaling in canine melanoma cells

“…Melanoma is a neoplastic disease with a poor prognosis that is highly invasive and frequently metastasizes in both humans and dogs [ 7 , 16 ]. Canine melanoma accounts about 5% of all canine neoplastic disease, with a median overall survival of 8–12 months after diagnosis [ 20 , 24 ]. Despite the use of standard treatment involving chemotherapy after surgical excision, the overall survival rates have remained low.…”