Enhancing the Anti-Tumor Efficacy of NK Cells on Canine Mammary Tumors through Resveratrol Activation

Simple Summary Mammary gland tumors are prevalent in canines, posing significant threats to their health and survival. With the limited efficacy of traditional treatments due to the high heterogeneity of these tumors, there is a growing focus on exploring new therapeutic avenues. Natural Killer cell-based immunotherapy has emerged as a promising approach in anti-tumor treatment, prompting research into optimization strategies. Resveratrol, a natural polyphenol compound, shows potential in regulating Natural Killer cell immune activity. However, the specific impact of Resveratrol-activated Natural Killer cells on canine mammary tumors and their therapeutic potential remain unclear. This study investigated the therapeutic potential of Resveratrol-activated Natural Killer cells in treating canine mammary tumors. Using various assays, including wound healing and flow cytometry, the study examined the impact of Resveratrol-pretreated Natural Killer cells on tumor cells in vitro and in a mouse model. The results demonstrate that Resveratrol enhances Natural Killer cells' ability to induce tumor cell death and inhibit tumor growth, migration, and invasion. Moreover, Resveratrol boosts Natural Killer cell recruitment to other immune cells in the body. Overall, Resveratrol shows promise in enhancing Natural Killer cell-mediated anti-tumor effects, suggesting a potential avenue for optimizing immunotherapy for canine mammary tumors and improving treatment efficacy.Abstract In order to explore the therapeutic effect of Resveratrol (Res)-activated Natural Killer (NK) cells on canine mammary tumors, this study employed a range of assays, including wound healing, colony formation, Transwell, flow cytometry, and Western blot experiments, to investigate the impact of Res-pretreated NK cells on canine mammary tumor cells in vitro. Additionally, a tumor-bearing mouse model was utilized to further analyze the therapeutic effects of Res-pretreated NK cells in vivo. The results showed that Res enhances the capacity of NK cells to induce apoptosis, pyroptosis, and ferroptosis in canine breast tumor cells, while also augmenting their influence on the migration, invasion, and epithelial-mesenchymal transition of these cells. Furthermore, pretreatment of NK cells with Res significantly amplified their inhibitory effect on breast tumor growth in vivo and promoted tumor tissue apoptosis. Additionally, Res enhanced the recruitment of NK cells to other immune cells in the body. In summary, Res has been shown to enhance the anti-breast-tumor effect of NK cells both in vitro and in vivo, offering a new avenue for optimizing immunotherapy for canine breast tumors.