Myeloid cell subsets that express latency-associated peptide promote cancer growth by modulating T cells
Year: 2021
Type: article
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-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.
Source: iScience
Authors: 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
Institutions: Brigham and Women's Hospital, Harvard University, Jounce Therapeutics (United States), Massachusetts Institute of Technology, National Institutes of Health, National Cancer Institute, Center for Cancer Research, Northwestern University, University of Colorado Boulder, University of Colorado Anschutz, University of New Mexico, Case Western Reserve University
Language: English
Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,000
Awards: MICRORNA CONTROL OF INFLAMMATORY AND REGULATORY T CELLS IN CENTRAL NERVOUS SYSTEM AUTOIMMUNITY, The pathogenic role of miR-92a in the regulation of T helper cell responses in EAE and MS, Development of novel PD1 agonist therapeutic strategies for multiple sclerosis, MicroRNA control of tumor-promoting inflammation in colon cancer
OpenAlex ID: W3210219649