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

ABSTRACT: 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-b on their surface, LAPHi MCs, that stimulate Foxp3+ Tregs while inhibiting effector T cell proliferation and function. Blocking TGF-b inhibits the tolerogenic ability of LAPHi MCs. Furthermore, adoptive transfer of LAPHi MCs promote Treg accumulation and tumor growth in vivo. Conversely, anti-LAP antibody, which reduces LAPHi MCs, slows cancer progression. Single-cell RNA-Seq analysis on tumor-derived immune cells revealed LAPHi 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 LAPHi MCs promote tumor growth and offer therapeutic intervention to target these cells in cancer.

ORGANISM(S): Mus musculus

PROVIDER: GSE174077 | GEO | 2021/11/24

REPOSITORIES: GEO

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