A single-cell transcriptomic study reveals immune suppressive cancer cell-immune cell interactions in the triple negative canine breast cancers

Abstract

Clinical trials show promising outcomes for dogs with advanced solid tumors following treatment with immune checkpoint inhibitors (ICIs). Triple-negative breast cancer (TNBC) is very aggressive with very low response rates to ICIs. No study defines how canine TNBC interacts with the immune system within the tumor microenvironment, which is investigated in this study at the single cell level. Single cell RNA sequencing (scRNA-seq) datasets, including 6 groups of 30 dogs, were subject to integrated bioinformatic analysis. Immune modulatory TNBC subsets were identified by functional enrichment with immune-suppressive gene sets, including anti-inflammatory and M2-like macrophages. Key genes and immune-suppressive signaling pathways for TNBC included angiogenesis and leukocyte chemotaxis. Interactome analysis identified significant interactions between distinct subsets of cancer cells and effector T cells, suggesting T cell suppression. This is the first study to define immune-suppressive cancer cell subsets at the single-cell level, revealing potential mechanisms by which TNBC induces immune evasion in dogs.