Barking up the right tree: Immune checkpoint signatures of human and dog cancers

Abstract

In the quest for improved therapeutics targeting immune checkpoints (ICs), we turn to spontaneously developing dog (canine) cancers, some of which genetically and clinically mirror the human counterparts. Despite its potential, canine cancer immunology remains largely unexplored. Here, we examine the RNA-seq-based expression of 44 ICs across 14 canine cancer types and an extensive human dataset. We unveil diverse canine IC expression patterns and unique human IC signatures that reflect the histological type and primary site of cancer. We uncover a striking similarity between canine brain cancers, osteosarcoma, and their human counterparts, identifying them as prospective immunotherapy models. Four ICs - CD160, A2AR, NKG2A, and OX40 - are key to the differences observed between species. We also find that individual human IC signatures vary in how well they align with their respective cancer types, a pattern that may influence future approaches to personalized therapy. This exploration highlights aspects of canine and human cancer immunology that warrant further study, setting the stage for discoveries at their crossroads.