文章基本信息

标题：Myeloid cell subsets that express latency-associated peptide promote cancer growth by modulating T cells
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作者：Galina Gabriely ; Duanduan Ma ; Shafiuddin Siddiqui 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：11
页码：1-25
DOI：10.1016/j.isci.2021.103347
语种：English
出版社：Elsevier
摘要：SummaryMyeloid 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 LAPHiMCs that stimulate Foxp3+Tregs while inhibiting effector T cell proliferation and function. Blocking TGF-β inhibits the tolerogenic ability of LAPHiMCs. Furthermore, adoptive transfer of LAPHiMCs promotes Treg accumulation and tumor growthin vivo. Conversely, anti-LAP antibody, which reduces LAPHiMCs, slows cancer progression. Single-cell RNA-Seq analysis on tumor-derived immune cells revealed LAPHidominated 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 LAPHiMCs promote tumor growth and offer therapeutic intervention to target these cells in cancer.Graphical abstractDisplay OmittedHighlights•Several myeloid cell subsets express surface LAP•Myeloid cells that express surface LAP possess immunosuppressive properties•LAP expressing myeloid cells induce Tregs and inhibit effector T cell function•LAP expressing myeloid cells promote tumor growthImmunology; Cancer