Feline mammary carcinoma (FMC) is a particularly lethal form of cancer in domestic cats, with 80-90% of FMC being highly malignant and metastatic. Feline patients are frequently affected by metastasis at the time of diagnosis, and survival times generally do not exceed a year despite broad resection and chemotherapy. Regrettably, very little improvements have been made in recent years. The main preventative approaches remain early spaying and avoiding the use of carcinogenic oral contraceptive hormones in queens (i.e. megestrol acetate). Despite the relative efficacy of these protective approaches when properly enforced, FMC unfortunately remains the 3rd most common feline cancer, and the leading cause of feline cancer-associated deaths. Because prevention is not sufficient, and since treatments are limited and provide short survival times, identifying additional avenues to improve patient treatment and disease outcome is necessary. In human medicine, immune checkpoint blockade (ICB) therapy has revolutionized the approach to cancer treatment. Some cancers, such as metastatic melanoma and non-small cell lung cancer, have shown encouraging response rates with long-term remission. Triple-negative breast cancer (TNBC) patients respond to some extent to anti-PD1 ICB therapy, though heterogeneously (5-30%). Recently, FMC has gained traction as a translational model that is biologically analogous to human TNBC and HER2-positive breast cancer. Thus, ICB therapy intuitively appears as an attractive treatment alternative for FMC. However, the heterogeneity of response rates observed in TNBC patients evidently raises concern for efficacy in feline patients. Over the past decade, the epithelial-mesenchymal transition (EMT) was identified as a main factor of resistance to immunotherapy in human breast cancer (HBC) patients. EMT is a physiological embryonic process that is aberrantly activated in BC, where it potentiates the ability of neoplastic cells to migrate and metastasize in addition to driving drug resistance. Importantly, tumors that undergo EMT foster an immunosuppressive tumor microenvironment (TME). Thus, EMT is a major mechanism of immune escape and directly correlates with resistance to ICB therapy. In a pilot study conducted on patient-derived samples, we have already demonstrated that EMT is associated with T-cell exclusion and intra-tumoral immunosuppressive macrophages infiltration in FMC. We thus hypothesize that the tight interplay between EMT and immunosuppressive TME can be translated to domestic cats and reveal whether feline patients will benefit from ICB therapy. This will be achieved by (i) evaluating a larger number of patient-derived formalin-fixed, paraffin-embedded FMC samples to refine our findings; (ii) characterizing readily available FMC cell lines; and (iii) establishing novel patient-derived FMC cell lines. This work will help better design feline patients’ access to more-personalized treatments in a new era of veterinary medicine that is slowly embracing individualized patient approaches, and generate improved disease outcomes. In the long term, we further envision that the EMT and immune-infiltration dynamics uncovered in this work will be applicable to other types of feline carcinomas.