Trem-1−/− mice tumor models exhibited TREM-1’s therapeutic potential in cancer. Trem-1−/− mice showed slower growth of melanoma (B16F10) and fibrosarcoma (MCA205) tumors. More single-cell RNA-Seq and functional experiments of Trem-1−/− tumor infiltrates indicated that myeloid-derived suppressor cells (MDSCs) have a lower immunosuppressive potential and higher PD-1 expression on CD8+ T cells. Here, CD8A is linked to melanoma.