Canine Melanoma Immunology and Immunotherapy: Relevance of Translational Research.

Lidia Tarone,Davide Giacobino,Paolo Buracco,Soldano Ferrone,Mariateresa Camerino,Federica Cavallo,Federica Riccardo

doi:10.3389/fvets.2022.803093

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.

Highlights

The interplay between the immune system and cancer has been widely investigated for over a century and has provided the groundwork for the emerging field of research known as immunooncology
We have focused our attention on chondroitin sulfate proteoglycan 4 (CSPG4), as a promising tumor-associated antigen to target for effective anticancer vaccination against both canine and human melanoma
On our side, considering that human CSPG4+ melanoma cells release small extracellular vesicles (SEVs) that carry high levels of CSPG4 [111, 129], we investigated its presence in canine-melanoma-cell-derived SEVs

Summary

INTRODUCTION

The interplay between the immune system and cancer has been widely investigated for over a century and has provided the groundwork for the emerging field of research known as immunooncology. Anti-PD-1 mAbs tested in canine cancer patients, including OMM cases, exerted a significant effect on the inhibition of the PD-1/PD-L1 axis in pilot clinical studies and exhibited remarkable anti-tumor activity, resulting in the increased survival of treated dogs, compared to conventionally treated controls [45, 47]. The combination of trimodal radiotherapy and intratumoral immunocytokine vaccination has been tested in advanced stage tumor-bearing dogs, including melanoma cases, and has preliminarily showed to induce positive immunomodulatory effects within the primary tumor [100] This result provides a starting point for investigating the diagnostic and prognostic predictive value of B7-H3 in circulating SEVs in melanoma bearing-dogs, with relevant translational implications for human immunotherapy

DISCUSSION

Findings

DATA AVAILABILITY STATEMENT