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
Materias:	Immunology Cancer Science Q
Acceso en línea:	https://doaj.org/article/cd2b4250e05d4e979dda9bd8430b32ec
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spelling	oai:doaj.org-article:cd2b4250e05d4e979dda9bd8430b32ec2021-11-20T05:10:18ZMyeloid cell subsets that express latency-associated peptide promote cancer growth by modulating T cells2589-004210.1016/j.isci.2021.103347https://doaj.org/article/cd2b4250e05d4e979dda9bd8430b32ec2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S258900422101316Xhttps://doaj.org/toc/2589-0042Summary: 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.Galina GabrielyDuanduan MaShafiuddin SiddiquiLinqing SunNathaniel P. SkillinHadi Abou-El-HassanThais G. MoreiraDustin DonnellyAndre P. da CunhaMai FujiwaraLena R. WaltonAmee PatelRajesh KrishnanStuart S. LevineBrian C. HealyRafael M. RezendeGopal MurugaiyanHoward L. WeinerElsevierarticleImmunologyCancerScienceQENiScience, Vol 24, Iss 11, Pp 103347- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunology Cancer Science Q
spellingShingle	Immunology Cancer Science Q 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 Myeloid cell subsets that express latency-associated peptide promote cancer growth by modulating T cells
description	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.
format	article
author	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
author_facet	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
author_sort	Galina Gabriely
title	Myeloid cell subsets that express latency-associated peptide promote cancer growth by modulating T cells
title_short	Myeloid cell subsets that express latency-associated peptide promote cancer growth by modulating T cells
title_full	Myeloid cell subsets that express latency-associated peptide promote cancer growth by modulating T cells
title_fullStr	Myeloid cell subsets that express latency-associated peptide promote cancer growth by modulating T cells
title_full_unstemmed	Myeloid cell subsets that express latency-associated peptide promote cancer growth by modulating T cells
title_sort	myeloid cell subsets that express latency-associated peptide promote cancer growth by modulating t cells
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/cd2b4250e05d4e979dda9bd8430b32ec
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Myeloid cell subsets that express latency-associated peptide promote cancer growth by modulating T cells

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