Immunotherapy has become a critical pillar in cancer treatment, offering durable responses in some patients. However, its efficacy is limited by resistance, with only a small subset of patients benefiting from current therapies targeting PD-1/PD-L1 pathways[1,2]. Therefore, there is an urgent need to identify additional immune markers that could serve as therapeutic targets. In our study, we focused on a novel immune checkpoint ligand 4 (ICL 4) and evaluated its expression in breast cancer patient samples using qRT-PCR and immunohistochemistry (IHC). Knockdown of this ligand was performed to assess its functional role in migration, clonogenicity, apoptosis, and tumor immunity. The immunomodulatory effects were further investigated by coculturing the knockdown cells with T cells, and further cytokine levels were measured using qRT-PCR. Our results demonstrated significant expression of the checkpoint ligand in breast cancer tissues. Silencing its expression led to a notable increase in immunostimulatory cytokines. These findings suggest that this ligand contributes to immune evasion and that its inhibition could enhance anti-tumor immune responses. This study highlights the potential of targeting this novel immune checkpoint ligand to overcome resistance to existing immunotherapies and improve treatment outcomes in breast cancer patients. Further research is warranted to explore its clinical relevance and therapeutic applications, including in additional related cancers such as ovarian cancer.