title: The Ribosomal Protein S19 Suppresses Antitumor Immune Responses via the Complement C5a Receptor 1.
abstract: Relatively little is known about factors that initiate immunosuppression in tumors and act at the interface between tumor cells and host cells. In this article, we report novel immunosuppressive properties of the ribosomal protein S19 (RPS19), which is upregulated in human breast and ovarian cancer cells and released from apoptotic tumor cells, whereupon it interacts with the complement C5a receptor 1 expressed on tumor infiltrating myeloid-derived suppressor cells. This interaction promotes tumor growth by facilitating recruitment of these cells to tumors. RPS19 also induces the production of immunosuppressive cytokines, including TGF-β, by myeloid-derived suppressor cells in tumor-draining lymph nodes, leading to T cell responses skewed toward Th2 phenotypes. RPS19 promotes generation of regulatory T cells while reducing infiltration of CD8+T cells into tumors. Reducing RPS19 in tumor cells or blocking the C5a receptor 1-RPS19 interaction decreases RPS19-mediated immunosuppression, impairs tumor growth, and delays the development of tumors in a transgenic model of breast cancer. This work provides initial preclinical evidence for targeting RPS19 for anticancer therapy enhancing antitumor T cell responses.
authors.affiliation: Department of Immunotherapeutics and Biotechnology, School of Pharmacy, Texas Tech University Health Science Center, Abilene, TX 79601; maciej.markiewski@ttuhsc.edu magdalena.karbowniczek@ttuhsc.edu.
authors.forename: Maciej M
authors.identifier: 0000-0002-8271-8918
authors.initials: MM
authors.lastname: Markiewski
authors.affiliation: Department of Immunotherapeutics and Biotechnology, School of Pharmacy, Texas Tech University Health Science Center, Abilene, TX 79601.
authors.forename: Surya Kumari
authors.initials: SK
authors.lastname: Vadrevu
authors.affiliation: Department of Immunotherapeutics and Biotechnology, School of Pharmacy, Texas Tech University Health Science Center, Abilene, TX 79601.
authors.forename: Sharad K
authors.identifier: 0000-0001-7743-3910
authors.initials: SK
authors.lastname: Sharma
authors.affiliation: Department of Immunotherapeutics and Biotechnology, School of Pharmacy, Texas Tech University Health Science Center, Abilene, TX 79601.
authors.forename: Navin Kumar
authors.initials: NK
authors.lastname: Chintala
authors.affiliation: Department of Immunotherapeutics and Biotechnology, School of Pharmacy, Texas Tech University Health Science Center, Abilene, TX 79601.
authors.forename: Shanawaz
authors.initials: S
authors.lastname: Ghouse
authors.affiliation: Department of Immunotherapeutics and Biotechnology, School of Pharmacy, Texas Tech University Health Science Center, Abilene, TX 79601.
authors.forename: Jun-Hung
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.|Australian Research Council Centre of Excellence in Advanced Molecular Imaging, The University of Queensland, Brisbane, Queensland 4072, Australia; and.
authors.forename: David P
authors.initials: DP
authors.lastname: Fairlie
authors.affiliation: Department of Microbiology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Yvonne
authors.identifier: 0000-0002-9406-4958
authors.initials: Y
authors.lastname: Paterson
authors.affiliation: Department of Immunotherapeutics and Biotechnology, School of Pharmacy, Texas Tech University Health Science Center, Abilene, TX 79601.
authors.forename: Aristotelis
authors.identifier: 0000-0001-7098-1391
authors.initials: A
authors.lastname: Astrinidis
authors.affiliation: Department of Immunotherapeutics and Biotechnology, School of Pharmacy, Texas Tech University Health Science Center, Abilene, TX 79601; maciej.markiewski@ttuhsc.edu magdalena.karbowniczek@ttuhsc.edu.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Karbowniczek
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000276:immunology*; D044087:Receptor, Anaphylatoxin C5a / Q000276:immunology*; D012269:Ribosomal Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: C488033:C5AR1 protein, human; D044087:Receptor, Anaphylatoxin C5a; D012269:Ribosomal Proteins; C040343:ribosomal protein S19