The tumor microenvironment (TME) fosters cancer progression by supporting the differentiation and proliferation of myeloid-derived suppressor cells (MDSCs), which play a critical role in suppressing immune responses and facilitating tumor growth. Recent findings by Dahal et al. reveal that platelet-activating factor (PAF), a lipid mediator elevated in the TME, contributes to the differentiation of neutrophils into immunosuppressive neutrophils. They showed that inhibiting PAF signaling reduces MDSC-mediated immunosuppression, thereby enhancing cytotoxic T-cell activity. This approach may improve cancer immunotherapy outcomes, particularly when combined with checkpoint blockade therapies, suggesting a promising avenue for therapeutic development.