Myeloid cell subsets that express latency-associated peptide promote cancer growth by modulating T cells

Myeloid suppressor cells promote tumor growth by a variety of mechanisms which are not fully characterized. We identified myeloid cells (MCs) expressing the latency-associated peptide (LAP) of TGF-β on their surface and LAP(Hi) MCs that stimulate Foxp3(+) Tregs while inhibiting effector T cell proliferation and function. Blocking TGF-β inhibits the tolerogenic ability of LAP(Hi) MCs. Furthermore, adoptive transfer of LAP(Hi) MCs promotes Treg accumulation and tumor growth in vivo. Conversely, anti-LAP antibody, which reduces LAP(Hi) MCs, slows cancer progression. Single-cell RNA-Seq analysis on tumor-derived immune cells revealed LAP(Hi) dominated cell subsets with distinct immunosuppressive signatures, including those with high levels of MHCII and PD-L1 genes. Analogous to mice, LAP is expressed on myeloid suppressor cells in humans, and these cells are increased in glioma patients. Thus, our results identify a previously unknown function by which LAP(Hi) MCs promote tumor growth and offer therapeutic intervention to target these cells in cancer.