Presentation of identical tumor antigen peptides by canine and human MHC class I

The increasing number of immunotherapies developed in the last two decades presents the need for an appropriate animal model to evaluate the efficacy of these treatments. The spontaneous nature of cancer in dogs and the common features they share with human malignancies make the dog a favorable translational model. The major histocompatibility complex (MHC) molecules in dogs are referred to as dog leukocyte antigens (DLA). Here, we introduce two antibodies for the characterization of the DLA class I immunopeptidome from primary canine tumors. We show that up to 55% of the peptides presented by tumor DLA are identical to peptides reported from common HLA class I molecules, displaying striking similarity in length and anchoring positions. Intriguingly, hundreds of these tumor DLA peptides are derived from well-established cancer-associated antigens. In summary, we demonstrate that canine and human MHC class I molecules are highly homologous in their antigen presentation function and peptide repertoire. These findings exhibit promising implications for advancing cancer immunotherapies and their translation from dogs to humans.