<p>Breast cancer remains the leading cause of cancer-related deaths among women worldwide. Combinatorial therapies are often employed to improve treatment efficacy and reduce the risk of recurrence. Hyperthermia (HT), a minimally invasive treatment, has shown potential to enhance immunotherapy outcomes. In the EMT6 breast tumor model, elevated CD200 expression is associated with tumor progression, and blockade of the CD200/CD200R signaling pathway has been reported to enhance anti-tumor immune responses. This study presents a preliminary evaluation of the therapeutic effects of local HT combined with anti-CD200 blockade in a preclinical mouse model. EMT6 tumors were established in Balb/c mice via subcutaneous inoculation. Local HT was applied on days 7, 8, and 9 post-inoculation, and anti-CD200 monoclonal antibody was administered intraperitoneally on days 7, 9, and 11. The combination therapy significantly reduced tumour progression and improved survival. Moreover, treated mice showed increased activation of CD8⁺ T cells in draining lymph nodes and enhanced tumor infiltration by T cells and natural killer (NK) cells, alongside a marked reduction in immunosuppressive regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). These findings highlight the need for further studies to validate and better understand the therapeutic potential of this combination approach in breast cancer.</p>