Could immune checkpoints PD-1/PD-L1, PD-L2 and CTLA-4 be valuable in the spontaneous canine model of breast cancer?

Immunotherapy has emerged as an auspicious new therapeutic modality in oncology, with immune checkpoint inhibitors showing promising results on several malignancies. Immune checkpoint molecules, such as PD-1 and its ligands (PD-L1 and PD-L2) and CTLA-4 represent a physiological mechanism to downregulate immune activity. This pathway seems to be used by different tumors to evade immune system and suppressing tumor-specific immune responses. Immune checkpoints expression in some tumors is related to higher malignancy and poor prognosis. The association of immune checkpoints with worst outcome has also been established specifically in human breast cancer. The evaluation of the role of immune checkpoints in canine mammary tumors is still very incipient. Therefore, further research will be needed in this field in order to provide new treatment and diagnosis targets and predictive factors with potential benefit for both human and animals. Herein, we provide an updated narrative review of the role of immune checkpoints in canine mammary tumors in comparison with breast cancer, emphasizing recent advances and the translational relevance of these pathways in comparative oncology.