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

Summary: 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 LAPHi MCs that stimulate Foxp3+ Tregs while inhibiting effector T cell...

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Autores principales: Galina Gabriely, Duanduan Ma, Shafiuddin Siddiqui, Linqing Sun, Nathaniel P. Skillin, Hadi Abou-El-Hassan, Thais G. Moreira, Dustin Donnelly, Andre P. da Cunha, Mai Fujiwara, Lena R. Walton, Amee Patel, Rajesh Krishnan, Stuart S. Levine, Brian C. Healy, Rafael M. Rezende, Gopal Murugaiyan, Howard L. Weiner
Formato: article
Lenguaje:EN
Publicado: Elsevier 2021
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Acceso en línea:https://doaj.org/article/cd2b4250e05d4e979dda9bd8430b32ec
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Sumario:Summary: 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 LAPHi MCs that stimulate Foxp3+ Tregs while inhibiting effector T cell proliferation and function. Blocking TGF-β inhibits the tolerogenic ability of LAPHi MCs. Furthermore, adoptive transfer of LAPHi MCs promotes 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.