Considering the above evidences and the lack of knowledge on the role of the PD-1/PD-L1 signaling pathway in tumor progression in the cat, this study aimed to: (i) quantify and compare the sPD-1 and sPD-L1 levels in animals with different mammary carcinoma subtypes and healthy controls; (ii) evaluate the PD-1 and PD-L1 expression in tumor-infiltrating lymphocytes (TILs) and cancer cells; (iii) test for statistical associations between serum PD-1, PD-L1, CTLA-4 and TNF-α levels; (iv) identify genomic mutations in the PD-L1 gene to validate future checkpoint-blocking therapies. This evidence concerns the gene HOXD13 and neoplasm.